1. 1-Cytoskeletal components of the neurons and their functions during axonregeneration. Neurons contain a cytoskeleton consisting of neurofibrils, which determine theshape of the soma and the various processes extending from it, and which transportsubstances throught the neuron Microtubules and microtubule associated proteins (MAP) 25-28nm are narrow longitudinal tubes present in all neuronal processes. The tubesmantain shape, and also transport molecules such as neuro-transmitters from the soma to the axon terminals (anterograd transport), or from the terminals to the soma (retrograde transport). There are at least two types of axonal transport: (a) rapid, 400nm (b) slow, at less than 1 mm dayMicrofilaments 5-7 nm present in high concentrations as a meshwork beneath the membrane of the axon. Actin is a important protein in axon development , and causes the movement of the growth cone. Are a proliferation of globulin actin (G-actin) in the axolemma of the synapse, depolarisation of the microfilaments is a prerequesite for releasing of the trasmitters from the synapse vesicles. Neurofilamets 10nm Are the most abundant of the fibrillar elements in the neuron, and form the bones of the cytoskeleton they are largely spaced, having tide arms that keep them appart and provide neuronal stability seem to be invoolved in the transport mechanisms 3 different types of neurons: 1. unipolar 2. bipolar – concentrated mainly in periphery 3. multi-polar – formed by alfa and beta tubules according to size: 1. Type I Golgi (large+long axons) 2. Type II Golgi (small+short axons)
2. 2-Types of axoplasmatic transports according direction and speed, theirfunctions in the intact neuron and during axon regeneration.Axonal Transport: Various secretory products produced in the cell body are carried to the axonterminals by special transport mechanism as in the same manner various constituents are carriedfrom the axon terminals to the cell body.Three main types of axonal transport are:⇒ fast anterograde transport⇒ slow anterograde transport⇒ fast retrograde transport.Fast anterograde transport is involved in the transport of materials that have afunctional role at the nerve terminals (e.g., precursors of peptide neurotransmitters,enzymes needed for the synthesis of small molecule neurotransmitters, andglycoproteins needed for reconstitution of the plasma membrane) are trasported fromthe cell body to the terminals. Polypeptides much larger than final peptideneurotransmitters (pre-propeptides) and enzymes needed for the synthesis of smallmolecule neurotransmitters are synthesized in the rough endoplasmic reticulum. Thevesicles formed in the Golgi apparatus for the axon terminals then become attached tothe microtubules and are transported by fast axonal transport (at a rate of 400 mm/d)into the nerve terminal. The rapid axonal transport depends on the microtubules. The microtubuleprovides a stationary track and a microtubule-associated ATPase (kinesin) forms across-bridge between the organelle to be moved and the microtubule. On one end,kinesin contains two globular heads that bind to the microtubule, and on the other end, ithas a fan-shaped tail that binds to the surface of an organelle. The organelle then movesby sliding of the kinesin molecule along the microtubuleSlow anterograde transport involves movement of neurofilaments and microtubulessynthesized in the cell body to the terminals at a rate of 5 mm/d. Soluble proteinstransported by this mechanism include actin, tubulin (which polymerizes to formmicrotubules), proteins that make up neurofilaments, myosin, and a calcium-bindingprotein (calmodulin).Fast retrograde transport is slower than the fast anterograde transport (about 200 mm/d). Rapid retrograde transport carries materials from the nerve terminals to the cellbody; the transported materials travel along microtubules. An example of transport by this mechanism is nerve growth factor (NGF), apeptide synthesized by a target cell and transported into certain neurons in order tostimulate their growth. Materials lying outside the axon terminals are taken up byendocytosis and transported to the cell body. Fast retrograde axonal transport is alsoinvolved in some pathological conditions. For example, the herpes simplex, polio, andrabies viruses and tetanus toxin are taken up by the axon terminals in peripheral nervesand carried to their cell bodies in the central nervous system (CNS) by rapid retrogradetransport.
3. 3-Types of the neuronal synapses, their classification according morphology and neurotransmitters. Synapses needed for communication e.g.interneuronal synapses or intermuscular Direct synapses in neuromuscular junction Indirect synapses in autonomic postganglionic synapse Synapses may be either: 1. interneuronal connections 2. connections between the neuron and effector Interneuronal connectionsaccording to position of connections: - axodendritic and axo somatic synapses - axo-axonal and dendro – dendritic synapsesaccording to effect on postsynaptic element -excitatory synapses -inhibitory synapsesaccording to transmission of the excitation - eletric synapses: - reduced extracellular space - transport of info by ionic flow -continuity of cytoplasm -chemical synapses: -presynaptic termination - postsynaptic element - active zone - synaptic cleft – no continuity between pre and post- synapses -increased extracellular space
4. - transport of info by neurotransmitters4-Glial cell types and their participation in the ontogenetic development of theCNSThe supporting cells located in the CNS are called neuroglia or simply glial cells. Theyare nonexcitable and more numerous (5 to 10 times) than neurons. Neuroglia have beenclassified into the following groups: astrocytes, oligodendrocytes, microglia, andependymal cells. ⇒ Astrocytes Among the glial cells, astrocytes are the largest and have a stellate (star-shaped)appearance because their processes extend in all directions. Their nuclei are ovoid andcentrally located. The astrocytes provide support for the neurons, a barrier against thespread of transmitters from synapses, and insulation to prevent electrical activity of oneneuron from affecting the activity of a neighboring neuron. They are further subdivided into the following subgroups:a) Protoplasmic Astrocytes: These cells are present in the gray matter in closeassociation with neurons. Because of their close association with the neurons, they areconsidered satellite cells and serve as metabolic intermediaries for neurons. They giveout thicker and shorter processes, which branch profusely. Several of their processesterminate in expansions called end-feet. Abutting of processes of protoplasmicastrocytes on the capillaries as perivascular end-feet is one of the anatomical features ofthe blood-brain barrierb) Fibrous AstrocytesThese glial cells are found primarily in the white matter between nerve fibers. Severalthin, long, and smooth processes arise from the cell body; these processes show littlebranching. Fibrous astrocytes function to repair damaged tissue, and this process mayresult in scar formation.c) MĂĽller CellsThese modified astrocytes are present in the retina.
5. ⇒ Oligodendrocytes These cells are smaller than astrocytes and have fewer and shorter branches.Their cytoplasm contains the usual organelles (e.g., ribosomes, mitochondria, andmicrotubules), but they do not contain neurofilaments. In the white matter,oligodendrocytes are located in rows along myelinated fibers and are known asinterfascicular oligodendrocytes. These oligodendrocytes are involved in themyelination process. The oligodendrocytes present in the gray matter are calledperineural oligodendrocytes. ⇒ Microglia These are the smallest of the glial cells. They usually have a few short branchingprocesses with thorn-like endings. These processes arising from the cell body give offnumerous spine-like projections. They are scattered throughout the nervous system.When the CNS is injured, the microglia become enlarged, mobile, and phagocytic. ⇒ Ependymal Cells Ependymal cells consist of three types of cells:a) Ependymocytes are cuboidal or columnar cells that form a single layer of lining inthe brain ventricles and the central canal of the spinal cord. They possess microvilli andcilia. The presence of microvilli indicates that these cells may have some absorptivefunction. The movement of their cilia facilitates the flow of the cerebrospinal fluid.b) Tanycytes are specialized ependymal cells that are found in the floor of the thirdventricle, and their processes extend into the brain tissue where they are juxtaposed toblood vessels and neurons. Tanycytes have been implicated in the transport of hormonesfrom the CSF to capillaries of portal system and from hypothalamic neurons to the CSF.
6. c) Choroidal epithelial cells are modified ependymal cells. They are present in thechoroid plexus and are involved in the production and secretion of CSF. They have tightjunctions that prevent the CSF from spreading to the adjacent tissues ⇒ PNS In the peripheral nervous system (PNS), Schwann cells provide myelin sheaths around axons. The myelin sheaths are interrupted along the length of the axons at regular intervals at the nodes of Ranvier. Thus, the nodes of Ranvier are + uninsulated and have a lower resistance. These nodes of Ranvier are rich in Na channels, and the action potential becomes regenerated at these regions. Therefore, the action potential traveling along the length of the axon jumps from one node of Ranvier to another. This type of propagation enables the action potential to conduct rapidly and is known as saltatory conduction. During the myelination, the axon comes in contact with the Schwann cell, which then rotates around the axon in clockwise or counterclockwise fashion. As the Schwann cell wraps around the axon, the cytoplasm becomes progressively reduced, and the inner layers of the plasma membrane come in contact and fuse together. ⇒ CNS Within the brain and the spinal cord, oligodendrocytes form the myelin sheathsaround axons of neurons. Several glial processes arise from one oligodendrocyte andwrap around a portion of the axon. The intervals between adjacent oligodendrocytes aredevoid of myelin sheaths and are called the nodes of Ranvier. Unlike in peripheralaxons, the process of an oligodendrocyte does not rotate spirally on the axon. Instead, itmay wrap around the length of the axon. The cytoplasm is reduced progressively, andthe sheath consists of concentric layers of plasma membrane. Unlike in peripheralnerves, one oligodendrocyte forms myelin sheaths around numerous (as many as 60)axons of diverse origins.
7. 5-Glial cell types and their involvement in the ontogenetic development of the PNS. Glial cells of PNS originate from neural crest cells (plate) Schwmann cells produce myelin sheaths around myelinated axons of PNS neurons. Glial cells provide support as well as protection for neurons Most glial derived from ectodermal tissue (particularly neural tube and crest) The exception is microglia- derive from mesoderm . sattelite cells surrond neuronal cell bodies in PNS Schwmann cells of PNS promote regeneration of peripheral neurons A myelinated nerve fiber is one that is surronded by a myelin sheath. In the CNS thesupporting cell is called oligodendrocytes, in the PNS is called Schmann cell. The development of the myelin sheath provides an indication of the constructionof its lamellae. The body of Schmann cell forms a rolled up sheet of paper in which theaxon become embebedded. The structure develops, its margins become approximatedand eventually meet together, which results in duplication of the cell membrane – themesaxon (pair of parallel plasma membranes of a Schwann cell, marking the point ofedge-to-edge contact by the Schwann cell encircling the axon). This becomes spirallybound around the axon, probably big movement of the Scwmann cell around theenclosed axon. The beginning of the duplication lies on the inner side of the myelinsheath (inner mesaxon) and its end on the outer side (outer mesaxon). Another type ofsupporting cell are the satellite cells. Both Schwmann cellas and satellite cells developfrom neural crest cells. Myelinating Schwann cells begin to form the myelin sheath in mammals duringfetal development and work by spiraling around the axon, sometimes with as many as100 revolutions. A well-developed Schwann cell is shaped like a rolled-up sheet ofpaper, with layers of myelin in between each coil. The inner layers of the wrapping,which are predominantly membrane material, form the myelin sheath while theoutermost layer of nucleated cytoplasm forms the neurolemma. Only a small volume ofresidual cytoplasm communicates the inner from the outer layers. This is seenhistologically as the Schmidt-Lantermann Incisure. Since each Schwann cell can cover
8. about a millimeter (0.04 inches) along the axon, hundreds and often thousands areneeded to completely cover an axon, which can sometimes span the length of a body.6-Describe Wallerian degeneration and different reactions of the glial cells inCNS and PNS following injury. ⇒ Neuronal Injury/ Injury of the Neuronal Cell Body The neuronal cell body may be damaged by disease, ischemia (lack of bloodsupply), or trauma. In the CNS (the brain and spinal cord), the debris produced by neuronal damageis phagocytosed by microglia. The adjacent fibrous astrocytes proliferate, and theneurons are replaced by scar tissue. In the PNS, macrophages are responsible for the removal of the debris producedby neuronal damage, and the scar tissue is produced by the proliferation of thefibroblasts. Necrotic cell death is caused by acute traumatic injury that involves rapid lysisof cell membranes. Necrotic cell death is different from apoptosis. Apoptosis is definedas a genetically determined process of cell death and is characterized by shrinkage ofthe cell, cellular fragmentation, and condensation of the chromatin. During the processof formation of tissues from undifferentiated germinal cells in the embryo(histogenesis), more neurons (about 2 times more) are formed than the neurons presentin the mature brain. The excess number of neurons is destroyed during the developmentby apoptosis. The mechanism of apoptosis involves activation of a latent biochemicalpathway that is present in neurons and other cells of the body. The cellular debris afterneuronal cell death is removed by phagocytosis, which involves transport of solidmaterial into the cells (e.g., microglia) that remove the debris by indentation of the cellmembrane of the phagocyte and formation of a vesicle. Pinocytosis is similar tophagocytosis, except that liquid material is removed. Exocytosis involves fusion of avesicle inside the nerve terminal (e.g., a vesicle containing a neurotransmitter) with theplasma membrane and transportation of the contents of the vesicle outside the nerveterminal.
9. ⇒ Axonal Damage/ Wallerian Degeneration This type of degeneration refers to the changes that occur distally to the site ofdamage on an axon. Because protein synthesis occurs primarily in the neuronal cellbody, the segment distal to the damaged site on the axon is affected profoundly.Initially, the axon swells up and becomes irregular. Later, the axon and the terminal arebroken down into fragments that are phagocytosed by adjacent macrophages andSchwann cells. Myelin is converted into fine drops of lipid material in the Schwanncells and is extruded from these cells; it is removed by macrophages in the PNS andmicroglial cells and invading macrophages in the CNS. Alterations may also be presentin the proximal segment of the axon up to the first node of Ranvier. ⇒ Chromatolysis Sectioning of an axon may produce changes in the cell body, and if the injury isclose to the cell body, the neuron may degenerate. The cell body swells up due to edemaand becomes round in appearance, and the Nissl substance gets distributed throughoutthe cytoplasm. The nucleus moves from its central position to the periphery due toedema. The degenerative changes start within hours and are complete within a relativelyshort time (about a week). ⇒ Anterograde Transneuronal Degeneration This type of degeneration occurs in the CNS when damage to a neuron results inthe degeneration of another postsynaptic neuron closely associated with the samefunction. For example, damage to an optic nerve results in the degeneration of thelateral geniculate neurons receiving inputs from this nerve. ⇒ Retrograde Transneuronal Degeneration This type of degeneration occurs in neurons sending inputs to an injured neuron.In this situation, terminals of the neuron synapsing with a chromatolytic neuronwithdraw and are replaced by processes of glial cells. The neuron, from which theinputs to the chromatolytic neuron arise, eventually degenerates.
10. ⇒ Recovery of Neuronal Injury (Regeneration) If the damage to the neurons is not severe and they survive the injury,regeneration is possible, but complete recovery may take as long as 3 to 6 months.Within about 3 weeks, the swelling of the cell subsides, the nucleus occupies a centralposition in the cell body again, and the Nissl bodies are normally distinguished. Theseevents indicate that protein synthesis has been restored in the neuronal cell body. Insevere damage, although sprouting occurs in axons in the CNS, this process ceaseswithin a short time (about 2 weeks). In this situation, normal functions of the neurons inthe CNS are not restored. However, in peripheral nerves, an axon can regeneratesatisfactorily if the endoneurial sheaths are intact. In this situation, the regeneratingaxons reach the correct destination, and the chances of recovery of function arereasonable. The growth rate of an axon has been estimated to be 2 to 4 mm per day.
11. 7-Describe developmental zones of the neural tube during histogenesis of the CNS, describecell populations originating from the neural crest. The nervous system develops from ectoderm, the surface layer of embryonictissue. By the third to fourth week of embryonic development, the notochord, ofmesodermal origin, induces the development of the neural plate. By the third to fourthweek of embryonic development, there is a high rate of cell proliferation. As such, theanterior part of the notochord (of mesodermal origin) begins to thicken, and thus, theneural plate is formed by the third week of fetal life. The neural plate continues tothicken over the following week and expands laterally. As it expands, the faster growinglateral edges of the plate accumulate in a dorsal position as neural folds. As this plategrows and widens, it forms a shallow groove along its longitudinal axis known as theneural groove. The posterior end of the neural plate, which is narrower than the anteriorend, will ultimately become the spinal cord, whereas the broader, anterior end willbecome the brain. As this plate grows and widens, the neural groove becomes deeper. Inthe process of its forming and deepening, some of the cells located in the lateral marginof the neural groove separate and migrate to a dorsal position to become the neuralcrest. As the embryo grows, the neural folds fuse along the midline, thus forming aneural tube. The neural tube consists of three layers: 1. an inner layer called the ventricular layer, which is in contact with the cavity of the neural tube; 2. an intermediate layer called the mantle layer; and 3. an outer layer called the marginal layer. The ventricular zone is the major proliferative layer and also the first layer of theforming neural tube to appear. The second layer to form is the marginal layer, followedby the mantle layer. Early in development, the wall of the neural canal becomesthickened, in part, by the formation of young or immature neurons that have yet tocompletely differentiate (sometimes called neurocytes) in the mantle layer. Because this
12. layer contains the primary cell bodies of neurons, it will ultimately become the graymatter of the spinal cord. Axons associated with cells in the mantle layer will grow intothe marginal layer. Histogenesis of CNS: 1. Ventricular zone -separates precursors for neurons and glial cells− -migration of nuclei to base of ventricular cells 2. Marginal zone− -no cell bodies - axons of neurons from intermediate zone invade this zone− 3. Intermediate zone− - forms a interface of ventricular and intermediate zones - no migration of nuclei Cell populations originating from neural crest: During folding of neural crest, groups of cells appear along neural groove, neural crest cells Some of these cells give rise sensory ganglia (dorsal root ganglia) cells of neural crest differentiate into Schwmann cells , pigment cells, meninges and odontoblasts.
13. 8-Describe trophic interactions among the neurons and their target tissue, describegeneral features of neurotrophic factors. Trophism refers to the ability of certain molecules called trophic (nutritional)factors, to promote cell survival. Neurotrophic factors are polypeptides that supportsurvival, growth, regeneration, and plasticity of neurons. Most types of neuron aregenerated in excessive numbers, followed later by the death of “surplus” cells soon afteraxons reach the vicinity of their target. This type of neuronal cell death is regarded to bea consequence of the competition for the limited amount of neurotrophic factorsreleased by target cells (e, g., embryonic muscle cells). This is an adaptive means ofadjusting the number of neurons of each type to the number of target cells to beinnervated. The “trophic effect” exerted on neurons is illustrated by the trophicinfluences of “taste nerve fibers” upon the taste buds. Not only do the gustatorynerve fibers convey taste information, but they also have critical roles in both themaintenance and regeneration of taste buds. Following transection of the gustatorynerve fibers, the taste buds degenerate. In time, if and when the transected fibersregenerate into the oral epithelium, new functional taste buds will differentiate fromepithelial cells, Presumably, only taste fibers elaborate the essential trophic factors toinduce the formation of new taste buds from the oral epithelium. Trophic activity couldoccur at any time from embryonic life through adulthood. Although a progressivereduction in activity occurs with age, it is never completely lost. In addition to trophiceffects, there are tropic effects. Tropism refers to the ability of certain molecules topromote or to guide the outgrowth and directional growth or extension of neuronalprocesses (axons and dendrites). Neurotrophins are a class among many neurotrophicfactors that have important roles in the survival of neurons and have widespread effectsthroughout the CNS and peripheral nervous system (PNS). Neurotrophins include nervegrowth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT3),and neurotrophin 4/5 (NT 4/5). Examples of related trophic factors include fibroblastgrowth factor (FGF), the epidermal growth factor family (EGF) and cytokines. Thecytokines (e.g., interleukin, a leukemia-inhibitory factor) are extracellular or membrane-anchored polypeptides that mediate communication between cells via cell surface
14. receptors. Trophic factors, as indicated, have roles in promoting the successive stages inthe cycle of neuronal differentiation, growth, survival, and programmed cell death 9-Selective neuronal death during ontogenic development of the nervoussystem; describe a mechanism and its significance. Programme cell death is an integral part of animal tissue development.Development of an organ or tissue is often preceded by the extensive division anddifferentiation of particular cell, with the resultant mass is then arranged in the correctform with help of apoptosis. Unlike cellular death (caused by hypoxia or other various injury), apoptosisresults in cell shrinkage and fragmentation. This allows the cells to be efficientlyphagocytosed and ther components removed without releasing of potentially harmfulintracellular substances into the surrounding tissue. If a neuron (and especially its DNA) gets damaged by a virus or a toxin,apoptosis destroys and silently removes these sick genes, which may serve to protectsurrounding healthy neurons. More importantly, apoptosis is a natural part ofdevelopment of the immature central nervous system. One of the many wonders of thebrain is the built-in redundancy of neurons early in development. These neuronscompete vigorously to migrate, innervate target neurons, and drink trophic factorsnecessary to fuel this process. Apparently, there is survival of the fittest, because up to50% of many types of neurons normally die in this time of brain maturation. Apoptosisis a natural mechanism to eliminate the unwanted neurons without making as big amolecular mess as doing it via necrosis. Cell death via apoptosis is a prominent feature in mammalian neuraldevelopment. Recent studies into the basic mechanism of apoptosis have revealedbiochemical pathways that control and execute apoptosis in mammalian cells. Proteinfactors in these pathways play important roles during development in regulating thebalance between neuronal life and death. Additionally, mounting evidence indicatessuch pathways may also be activated during several neurodegenerative diseases,resulting in improper loss of neurons.
15. 10-Describe molecular mechanisms for axon navigation to the target tissue duringdevelopment and regeneration of the nervous system. Molecular mechanisms of axon guidance: 1. Contact inhibition – adhesion (permissive and non-permissive substrates) 2. Fasciculation (small, involuntary muscle contractions due to spontaneous discharges) 3. Chemotropism (movement caused by chemical stimulus) Cellular and molecular mechanisms for regeneration of nervous system:Different reaction of the CNS and PNS neurons to injury of neural processes.PNS neurons: anabolic processes due to increased synthesis of cytoskeleton andmembrane proteins and increased synthesis of RNA.CNS neurons: reaction with distinct regressive mechanisms(atrophy) and destructionof neurons. Decreased synthesis if the RNA
16. 11-Describe structural components of the hematoencephalic barrier, functionalsignificance of HEB. Meningeal barriers is formed by arachnoid placed between intradural blood vessels and CSF in the subarachnoid space. Blood-brain barrier, which is located at the interface between the capillary wall and brain tissue. The blood-brain barrier consists of: (1) endothelial cells lining the capillary wall with tight junctions between them, (2) processes of astrocytes abutting on the capillaries as perivascular end-feet, (3) a capillary basement membrane. This arrangement of different cells or their processes prevents the passage of large molecules from the blood into the extracellular space between the neurons and neuroglia and forms the anatomical basis of the blood-brain barrier. One of the beneficial functions of the blood-brain barrier is to prevent entry of blood-borne foreign substances into the brain tissue. However, the existence of this blood-brain barrier also presents a problem when the goal is to deliver drugs into the CNS. In other organs, tight junctions do not exist between the neighboring endothelial cells lining the capillaries. The capillaries and the ependymal epithelial cells of the choroid plexus form the blood-CSF barrier between the blood and CSF. The presence of this barrier results in distinct differences of concentration of some molecules in the blood and CSF
17. 12-Describe the CNS liquid compartments and their barriers. Fluid (liquid) compartments: Interstitial fluid: bathing neurons and glial cells within CNS CSF: in subarachnoid space and ventricular system. Blood: in the meningeal vessels Intracellular fluid: in neurons and glial cells CSF: There are four main functions of the CSF. (1) The brain and spinal cordfloat in the CSF because the specific gravities of these central nervous system (CNS)structures are approximately the same. This buoyant effect of the CSF results inreduction of traction exerted upon the nerves and blood vessels connected with theCNS. (2) The CSF provides a cushioning effect on the CNS and dampens the effects oftrauma. (3) The CSF also serves as a vehicle for removal of metabolites from the CNS.(4) Under normal conditions, the CSF provides a stable ionic environment for the CNS.However, the chemical composition of the CSF may change in certain situations such asadministration of drugs that cross the blood-brain barrier. The cerebral barriers: Meningeal barriers: is formed by arachnoid placed between intradural blood vessels and CSF in the subarachnoid space
18. 13- Describe individual mechanisms of transportation throught thehematoencephalic barrier.Transport mechanisms of blood brain barrier (BBB)⇒ Passive diffusion: lipid soluble substances pass throught the barrier, such as O2, Co2, barbiturates, alcohol⇒ Facilitated diffusion: substances that penetrate membranes by carrier or mediated mechanisms. This category of transport carries more molecules and rapidly and without consumption of enegy.⇒ Active transport: consumption of energy, and uses carrier molecules. It proceeds against a concentration gradient. E.g amino acids or extracellular potassium. Moves molecules from the brain and CSF into blood plasma against a concentration gradient.⇒ Transcytosis: is selective transport by means of the coated vesicles that fuse to form trasnsendothelial canal, e.g. Fe bind transferin ehich has Fe receptors The combination of the specialized cell membrane of the endothelial cells linkedby intercellular tight junctions is the hallmark of the BBB. This duo effectively excludesby blocking the passage of many substances across the capillary wall. The permeabilityproperty can be enhanced by the state of phosphorylation of the proteins of the cell–celladherens junctions. The cadherin proteins of the adherens junctions also act as a sig-nalling component between endothelial cells through linkages with the cytoskeletal pro-tein filaments of the endothelial cells. The presence of so few pinocytotic vesicles with-in the endothelial cells is indicative that the transcellular movement by vesicles acrossthe BBB (transendocytosis) is both relatively deficient and slow. However, the selectivepassage of substances is related to the presence of high concentrations of carriermedi-ated transport systems that act as transporters for glucose, essential amino acids, otherrequired nutrients, and macromolecules. These ensure the passage of essential sub-stances from the blood to the CNSThe combination of the specialized cell membrane ofthe endothelial cells linked by intercellular tight junctions is the hallmark of the BBB.This duo effectively excludes by blocking the passage of many substances across the ca-pillary wall. The permeability property can be enhanced by the state of phosphorylationof the proteins of the cell–cell adherens junctions. The cadherin proteins of the adherensjunctions also act as a signalling component between endothelial cells through linkageswith the cytoskeletal protein filaments of the endothelial cells. The presence of so fewpinocytotic vesicles within the endothelial cells is indicative that the transcellular move-ment by vesicles across the BBB
19. 14- Describe the CNS structures without total hematoencephalic barrier and theirfunction. There are seven structures in the CNS that lack a blood-brain barrier. Calledcircumventricular organs, they are the area postrema, pineal body, subcommissuralorgan, subfornical organ, organum vasculosum of lamina terminalis (OVLT),neurohypophysis (the posterior pituitary gland), and the median eminence. They lack tight junctions in their capillaries. Instead, they have fenestratedcapillaries, capillary loops, and large perivascular spaces that permit the passage oflarger circulating molecules into the adjacent brain tissue. It is believed that somecirculating hormones consisting of large molecules reach their target areas in the brainvia the circumventricular organs. For example, the subfornical organ lies in the roof ofthe third ventricle. Blood-borne angiotensin II reaches the subfornical organ readilybecause of the lack of the blood-brain barrier in this organ and induces thirst for overallregulation of fluid balance and cardiovascular homeostasis. Functional effects⇒ Acts as homeostatic organs: e.g neurohypophyses releases oxitocin and vasopressin (ADH)⇒ Acts as as chemoreceptors e.g. Angiotensin II may act to increase blood pressure⇒ Acts as osmoreceptors⇒ The area postrema is the vomiting centre of the brain, detect noxious substances in the blood and stimulate vomiting in order to rid that substances from the body
20. 15- Measuring of the cerebral blood flow The metabolic demands of the brain must be met with the blood supply to thisorgan. Normal cerebral blood flow is about 50 mL/100 g of brain tissue/min. Thus, abrain of average weight (1500 g) has a normal blood flow of 750 mL/min. Even a briefinterruption of the blood supply to the CNS may result in serious neurologicaldisturbances. A blood flow of 25 mL/100 g of brain tissue/min constitutes ischemicpenumbra (a dangerously deficient blood supply leading to loss of brain cells). A bloodflow of 8 mL/100 g of brain tissue/min leads to an almost complete loss of functionalneurons. Consciousness is lost within 10 seconds of the cessation of blood supply to thebrain. Freks principle: Cerebral blood flow can be measured by determining the amount of nitrousoxide removed from the blood stream (Qx) per unit of time and dividing that value bythe difference between the concentration in the atrial blood (Ax) and the in the venousblood (Vx): Qx CBF= --------------- [Ax] - [Vx]Qx= amount of nitrous oxide removed from the bloodAx= concentration in atrial bloodVx= concentration in the venous bloodAverage blood flow in young adults is 54ml/100g/minAverage brain weight 1400g hence we have a blood flow to brain corresponding to756ml/minFactors that affect cerebral blood flow : 1) Intracranial pressure 2) Blood viscosity 3) Mean venous pressure 4) Mean atrial pressure 5) Constriction and dilation of cerebral arterioles
21. 16 – Blood flow in various parts of the brain Arterial supply of the brain: Blood supply to the brain is derived from two arteries: (1) the internal carotidartery and (2) the vertebral artery. These arteries and their branches arise in pairs thatsupply blood to both sides of the brain. The basilar artery is a single artery located in themidline on the ventral side of the brain. The branches of the basilar artery also arise inpairs. Internal Carotid Artery This artery arises from the common carotid artery on each side at the level of thethyroid cartilage and enters the cranial cavity through the carotid canal. Branches:⇒ The Ophthalmic Artery: enters the orbit through the optic foramen and gives rise to the central artery of the retina, which supplies the retina and cranial dura. Interruption of blood flow in the ophthalmic artery causes loss of vision in the ipsilateral eye.⇒ The Posterior Communicating Artery: arises at the level of the optic chiasm and travels posteriorly to join the posterior cerebral arteries. Small branches arising from this artery supply blood to the hypophysis, infundibulum, parts of the hypothalamus, thalamus, and hippocampus.⇒ The Anterior Choroidal Artery: arises near the optic chiasm and supplies the choroid plexus located in the inferior horn of the lateral ventricle, the optic tract, parts of the internal capsule, hippocampal formation, globus pallidus, and lateral portions of the thalamus.⇒ The Anterior Cerebral Artery: The anterior cerebral artery travels rostrally through the interhemispheric fissure. It supplies blood to the medial aspect of the cerebral hemisphere, including parts of the frontal and parietal lobes. This artery also supplies blood to the postcentral gyrus and precentral gyrus. Occlusion of one of the anterior cerebral arteries results in loss of motor control (paralysis) and loss of sensation in the contralateral leg. Other structures supplied by the anterior cerebral artery include the olfactory bulb and tract, anterior hypothalamus, parts of caudate nucleus, internal capsule, putamen, and septal nuclei.⇒ The Anterior Communicating Artery: at the level of the optic chiasm, the anterior communicating artery connects the anterior cerebral arteries on the two sides. A group of small arteries arising from the anterior communicating and anterior cerebral arteries penetrates the brain tissue almost perpendicularly and supplies blood to the anterior hypothalamus, including preoptic and suprachiasmatic areas.⇒ The Medial Striate Artery (Recurrent Artery of Heubner): arises from the anterior cerebral artery at the level of the optic chiasm and supplies blood to the anteromedial part of the head of the caudate nucleus and parts of the internal capsule, putamen, and septal nuclei. The medial striate and the lenticulostriate arteries penetrate the perforated substance.⇒ The Middle Cerebral Artery: at the level just lateral to the optic chiasm. Branches of the middle cerebral artery supply blood to the lateral convexity of the cerebral hemisphere including parts of the temporal, frontal, parietal, and occipital lobes.
22. Vertebro-Basilar Circulation:This system includes the two vertebral arteries, the basilar artery (which is formed bythe union of the two vertebral arteries), and their branches. This arterial system suppliesthe medulla, pons, mesencephalon, and cerebellum. Braches:⇒ The vertebral artery: on each side is the first branch arising from the subclavian artery. It enters the transverse foramen of the sixth cervical vertebrae, ascends through these foramina in higher vertebra, and eventually enters the cranium through the foramen magnum. In the cranium, at the medullary level, each vertebral artery gives off the anterior spinal artery, the posterior inferior cerebellar artery, and the posterior spinal artery.⇒ The Anterior Spinal Artery: at the confluence of the two vertebral arteries, two small branches arise and join to form a single anterior spinal artery. This artery supplies the medial structures of the medulla, which include the pyramids, medial lemniscus, medial longitudinal fasciculus, hypoglossal nucleus, and the inferior olivary nucleus.⇒ The Posterior Inferior Cerebellar Artery (PICA): arises from the vertebral artery and supplies the regions of the lateral medulla that include the spinothalamic tract, dorsal and ventral spinocerebellar tracts, descending sympathetic tract, descending tract of cranial nerve V, and nucleus ambiguus.⇒ The Posterior Spinal Artery (PSA): It is the first branch of the vertebral artery in the cranium in about 25% of cases. However, in a majority of cases (75%), it arises from the posterior inferior cerebellar artery. In the caudal medulla, this artery supplies the fasciculus gracilis and cuneatus as well as the gracile and cuneate nuclei, spinal trigeminal nucleus, dorsal and caudal portions of the inferior cerebellar peduncle, and portions of the solitary tract and dorsal motor nucleus of the vagus nerve.⇒ The Basilar Artery: The two vertebral arteries join at the caudal border of the pons to form the single basilar artery.⇒ The Anterior Inferior Cerebellar Artery (AICA): is the most caudal branch arising from the basilar artery. The AICA supplies the ventral and inferior surface of the cerebellum and lateral parts of the pons.⇒ The labyrinthine (internal auditory) artery: is usually a branch of the AICA and supplies the cochlea and labyrinth.⇒ The Pontine Arteries: Several pairs of pontine arteries arise from the basilar artery. Some pontine arteries (the paramedian arteries) enter the pons immediately and supply the medial portion of the lower and upper pons. Some pontine arteries (the short circumferential arteries) travel a short distance around the pons and supply substantia nigra and lateral portions of the midbrain tegmentum.⇒ The superior cerebellar artery: arises just caudal to the bifurcation of the basilar artery and supplies the rostral level of the pons, caudal part of the midbrain, and superior surface of the cerebellum. ⇒ The posterior cerebral arteries arise at the terminal bifurcation of the basilar artery. Branches of the posterior cerebral arteries supply most of the midbrain, thalamus, and subthalamic nucleus. Cerebral Arterial Circle (Circle of Willis)
23. The cerebral arterial circle surrounds the optic chiasm and the infundibulum of thepituitary. It is formed by the anastomosis of the branches of the internal carotid arteryand the terminal branches of the basilar artery. The anterior communicating arteryconnects the two anterior cerebral arteries, thus forming a semicircle. The circle iscompleted as the posterior communicating arteries arising from the internal carotidarteries at the level of the optic chiasm travel posteriorly to join the posterior cerebralarteries that are formed by the bifurcation of the basilar artery. The circle of Willis ispatent in only 20% of individuals. When it is patent, this arterial system supplies thehypothalamus, hypophysis, infundibulum, thalamus, caudate nucleus, putamen, internalcapsule, globus pallidus, choroid plexus (lateral ventricles), and temporal lobe.
24. 17- Regulation of cerebral circulation. Brain metabolism.Brain metabolism:3 metabolic factors have potent effect on control of cerebral blood flow (CBF) :⇒ Increase in [CO2] leads to increase of CBF. CO2 + H2O H2CO3 HCO3- + H+ AND the H+ causes the dilation of cerebral vessels⇒ Increase in H+ leads to increase in CBF⇒ Decrease in O2 leads increase CBF via vasodilationThe brain (2% of the total body weight) receives about 15% of the cardiac output andconsumes about 20% of the total O2 consumption.The brain is highly sensitive to disturbances of the blood supply. Ischaemia lastingseconds causes symptoms and lasting for few minutes causes irreversible damage.The caliber of the arterioles is regulated by:⇒ Local vasodilators; metabolites (e.g. CO2)~⇒ Vasoactive substances produced by the endothelium, circulating peptides such as angiotensin II⇒ Vasomotor nerves⇒ Autoregulation mechanisms (the systemic blood pressure increases, but the cerebral blood flow remains constant by: a) intraluminar pressure within the arterioles elicits direct myogenic responde b) hypocapnia causes arterial vasoconstrictionIntracranial pressure:⇒ cerebral vessels are compressed even if there is no increase in intracranial pressure⇒ any change in venous pressure causes a similar change in intracranial pressure. A rise in venous pressure decreases cerebral blood flow.⇒ Cerebreal circulation has strong sympathetic innervation extending from the superior cervical ganglion⇒ Brain extremely sensitive to hypoxia⇒ Ammonia very toxic to nerve cells and leaves the brain in the form of glutamine
25. 18- Formation and absorption of cerebrospinal fluid. Function of cerebrospinalfluid. Formation of the Cerebrospinal fluid: About 70% of the CSF present in the brain and spinal cord is produced by thechoroid plexuses. The remaining 30% of CSF, which is secreted by the parenchyma ofthe brain, crosses the ependyma (a single layer of ciliated columnar epithelial cellslining the ventricular system) and enters the ventricles. The formation of CSF is anactive process involving the enzyme carbonic anhydrase and specific transportmechanisms. The formation of the CSF first involves filtration of the blood through thefenestrations of the endothelial cells that line the choroidal capillaries. However, themovement of peptides, proteins, and other larger molecules from this filtrate into theCSF is prevented by the tight junctions that exist in the neighboring epithelial cells thatform the outer layer of the choroid plexus. Energy-dependent active transportmechanisms are present in the choroidal epithelium for transporting Na+ and Mg2+ ionsinto the CSF and for removing K+ and Ca2+ ions from the CSF. Water flows across theepithelium for maintaining the osmotic balance. Normally, the rate of formation of CSFis about 500 mL/day and the total volume of CSF is 90 to 140 mL, of which about 23mL is in the ventricles, and the remaining is in the subarachnoid space. Circulation: The movement of CSF is pulsatile. It flows from the lateral ventricles into thethird ventricle through the foramina of Monro where it mixes with more CSF. Then, itflows through the cerebral aqueduct (aqueduct of Sylvius) into the fourth ventricle,where additional CSF is secreted. The fluid leaves the ventricular system via theforamina of Luschka and Magendie and enters the cerebellomedullary cistern (cisternamagna). The CSF then travels rostrally over the cerebral hemisphere where it enters thearachnoid villi. Absorption: is made throught the arachidonic vili. The CSF drains into duralvenous sinuses, there are valves here, so fluid flows only from vili to veins wherepressure difference is appropriate. Functions: There are four main functions of the CSF. (1) The brain and spinal cord float in the CSF because the specific gravities ofthese central nervous system (CNS) structures are approximately the same. Thisbuoyant effect of the CSF results in reduction of traction exerted upon the nerves andblood vessels connected with the CNS. (2) The CSF provides a cushioning effect on the CNS and dampens the effects oftrauma. (3) The CSF also serves as a vehicle for removal of metabolites from the CNS. (4) Under normal conditions, the CSF provides a stable ionic environment forthe CNS. Composition:Normally, very little protein is present in the CSF, and this is the primary differencebetween CSF and blood serum. The concentrations of glucose, as well as
26. 19 – Resting potential of the neuron Resting membrane potential: When a neuron is not generating actionpotentials, it is at rest. When the neuron is at rest, its cytosol along the inner surface ofits membrane is negatively charged compared with the charge on the outside. Typically,the resting membrane potential (or resting potential) of a neuron is -65 millivolts (mV). The potential difference across the cell membrane during resting state is calledthe resting membrane potential. The lipid bilayer of the neuronal membrane maintainsthis separation of charges by acting as a barrier to the diffusion of ions across themembrane. The ion concentration gradients across the neuronal membrane areestablished by ion pumps that actively move ions into or out of neurons against theirconcentration gradients. The selective permeability of membranes is due to the presenceof ion channels that allow some ions to cross the membrane in the direction of theirconcentration gradients. The ion pumps and ion channels work against each other in thismanner. If the neuronal membrane is selectively permeable to only a K+ ion, this ionwill move out of the neuron down its concentration gradient. Therefore, more positivecharges accumulate outside the neuron. The fixed negative charges inside the neuronimpede the efflux of positively charged K+ ions, and excess positive charges outside theneuron tend to promote influx of the K+ ions into the neuron due to the electrostaticforces. The opposite charges attract, while similar charges repel each other. Thus, twoforces are acting on the flow of K+ ions out of the neuron; a higher concentration insidethe neuron (concentration gradient) tends to expel them out of the neuron, while theelectrostatic forces tend to prevent their flow out of the neuron. When the two opposing forces are equal, K+ concentrations inside and outsidethe neuron are in equilibrium. The value of the membrane potential at this time is calledthe K+ equilibrium potential. Thus, if the neuronal membrane contained only K+channels, the resting membrane potential would be determined by the K+ concentrationgradient and would be equal to the equilibrium potential for K+ ions (approximately -80mV). However, as stated earlier, the resting membrane potential of a neuron is usually-65 mV. This is because neurons at rest are permeable to the Na+ ion also. The Na+ ionstend to flow into the neuron due to two forces: (1) concentration gradient of Na+ ions(extracellular Na+ concentration is much higher than its intracellular concentration) and(2) electrostatic forces (there is an excess of positive charges outside and an excess ofnegative charges inside the neuron). Due to the influx of Na+ ions, the resting membranepotential deviates from that of the K+ equilibrium potential (i.e., it becomes -65 mVinstead of -80 mV). However, the membrane potential does not reach the equilibrium potential for +Na . The reason for the neurons inability to attain a resting membrane potential closerto the Na+ equilibrium potential is that the number of open nongated Na+ channels ismuch smaller than the number of open nongated K+ channels in the resting state of aneuron. The permeability of Na+ is small despite large electrostatic and concentrationgradient forces tending to drive it into the neuron. To maintain a steady restingmembrane potential, the separation of charges across the neuronal membrane must bemaintained at a constant. This is accomplished by the Na+-K+ pump described earlier. Goldman equation: since the neuronal membrane is permeable to more thanone ion, the goldman equation is used to calculate membrane potential. This equationtakes into account the contribution of the permeability of each ion and its extra- andintracellular concentration. Nerst equation: is used to calculate equilibrium potential of an ion that ispresent on both sides of the cell membrane.
27. 20- Receptor, synaptic and action potential-descriptionReceptor potential: whatever the stimulus that excites the receptor, its immediateeffect is to arrange the membrane potential of the receptor. This change is calledreceptor potential.Different receptors can be excited, either: a) By mechanical deformation that stretches the receptor membrane and opens ion channels. b) By application of a chemical to the membrane c) By change of temperature d) By eletromagnetic radiationWhen the receptor potential rises above the threshold for eliciting an action potential,the the action potential begins to appear. The more the receptor potential rises above thethreshold level, the greater becomes the action potential frequencySynaptic potential: an interaction of a transmitter on postsynaptic neuron initiates asynaptic potential.Can be either: EPSP (excitatory postsynaptic potential) IPSP (inhibitory postsynaptic potential)Action potential: rapid change in the membrane potential. It begins with a suddenchange from the normal resting membrane potential to a positive membrane potential. When a neuron receives an excitatory input, the neuronal membrane isdepolarized, resulting in an opening of some voltage-gated Na+ channels and influx ofNa+ . The accumulation of positive charges due to influx of Na+ promotes depolarizationof the neuronal membrane. When the membrane potential reaches threshold potential,the chances of generating an action potential are about 50%. However, when themembrane is depolarized beyond the threshold potential, a sufficient number of voltage-gated Na+ channels open, relative permeability of Na+ ions is greater than that of K+ions, and action potentials are generated with certainty. During the rising phase of the action potential, there is a rapid depolarization ofthe membrane due to increased permeability of Na+. The depolarization continues sothat the membrane potential approaches the Na+ equilibrium potential. The part of theaction potential where the inside of the neuron is positive relative to the outside is calledthe overshoot. Towards the end of the rising phase of the action potential, voltage-gatedNa+ channels are inactivated, and the influx of Na+ through these channels is stopped.During the falling phase of the action potential, the neuron is repolarized by opening ofvoltage-gated K+ channels, which allows increased efflux of K+ from the neuron throughthese channels. The opening of voltage-gated K+ channels is also caused bydepolarization of the neuronal membrane. Because these voltage-gated K+ channelsopen with a delay (about 1 msec) after the membrane depolarization and their openingrectifies the membrane potential, they are called delayed rectifier K+ channels. At theend of the falling phase, the membrane potential is more negative than the restingpotential because of increased K+ permeability caused by the opening of the delayedrectifier K+ channels in addition to the already present resting K+ permeability throughnongated channels. The permeability is closer to the equilibrium potential of K+ becausethere is little Na+ permeability during this period. This portion of the action potential iscalled after-hyperpolarization or undershoot. Once after-hyperpolarization has occurred,the resting membrane potential is restored gradually as the voltage-gated K+ channelsclose again.
28. 21 – Ionic basis of membrane potential changes The resting membrane potential of a neuron is usually -65 mV. At rest, Na+influx into the neuron through open nongated Na+ channels is balanced by the efflux ofK+ through open nongated K+ channels. Thus, the membrane potential remains constantcloser (but not equal) to the K+ equilibrium. When a neuron receives an excitatory input, the neuronal membrane isdepolarized, resulting in an opening of some voltage-gated Na+ channels and influx ofNa+. Na+ channels are normally closed. The accumulation of positive charges due toinflux of Na+ promotes depolarization of the neuronal membrane. When the membranepotential reaches threshold potential, the chances of generating an action potential areabout 50%. However, when the membrane is depolarized beyond the thresholdpotential, a sufficient number of voltage-gated Na+ channels open, relative permeabilityof Na+ ions is greater than that of K+ ions, and action potentials are generated withcertainty. Generation of an action potential is an all-or-nothing phenomenon. Becausethe concentration of Na+ channels is relatively high at the axon hillock, this is the site ofgeneration of action potentials in a neuron. During the rising phase of the action potential generation, there is a rapiddepolarization of the membrane due to increased permeability of Na+. Thedepolarization continues so that the membrane potential approaches the Na+ equilibriumpotential. The part of the action potential where the inside of the neuron is positiverelative to the outside is called the overshoot. Towards the end of the rising phase of theaction potential, voltage-gated Na+ channels are inactivated, and the influx of Na+through these channels is stopped.During the falling phase of the action potential, the neuron is repolarized by opening ofvoltage-gated K+ channels, which allows increased efflux of K+ from the neuron throughthese channels. The opening of voltage-gated K+ channels is also caused bydepolarization of the neuronal membrane. Because these voltage-gated K+ channelsopen with a delay (about 1 msec) after the membrane depolarization and their openingrectifies the membrane potential, they are called delayed rectifier K+ channels. At theend of the falling phase, the membrane potential is more negative than the restingpotential because of increased K+ permeability caused by the opening of the delayedrectifier K+ channels in addition to the already present resting K+ permeability throughnongated channels. The permeability is closer to the equilibrium potential of K+ becausethere is little Na+ permeability during this period. This portion of the action potential iscalled after-hyperpolarization or undershoot. Once after-hyperpolarization has occurred,the resting membrane potential is restored gradually as the voltage-gated K+ channelsclose again. The sodium channel exists in the following three states: resting, activated, orinactivated. • Resting state: During this state, the activation gate closes the channel pore while the inactivation gate is open. With the channel pore closed, Na+ cannot flow into the neuron. • Activated state: During the rising phase of action potential, both activation and inactivation gates are open, and Na+ ions flow into the neuron. • Inactivated state: During this state, the inactivation gate closes the channel pore while the activation gate is still open. Even though the activation gate is open, Na+ cannot flow into the neuron. The neuron cannot be activated until the
29. 22- Ion channels in neurons – their distributionsIon Channels:. Ion channels are made up of proteins that are embedded in the lipid bilayer ofthe neuronal membrane across which they span. They are characterized by the followinggeneral properties. • The flow of ions through the channels does not require metabolic energy; the flow is passive. • The electrochemical driving force across the membrane, but not the channel itself, determines the direction and eventual equilibrium of this flow. • The ionic charge determines whether a channel allows an ion to flow through; some channels allow cations while others allow anions to flow through them. • Most cation-selective channels allow only one ion species (e.g., Na+ or K+ or Ca2+) to flow through them. However, some channels allow more than one ion species to flow through them. For example, when L-glutamate (an excitatory amino acid neurotransmitter) activates an N-methyl-D-aspartic acid (NMDA) receptor, both Na+ and Ca2+ ions flow through the NMDA receptor channel into the neuron. • Most anion-selective channels allow only Cl- to flow through them. • Some blockers can prevent the flow of ions through the ion channels. For example, phencyclidine (PCP, or Angel Dust) blocks the NMDA receptor channel. Classification of Ion Channels: Nongated Channels: Although nongated channels are capable of opening as well as closing, most of thetime they are in the open site. They control the flow of ions during the restingmembrane potential. Examples include nongated Na+ and K+ channels that contribute tothe resting membrane potential. Gated Channels: These channels are also capable of opening as well as closing. All gated channelsare allosteric proteins The channels that are opened or closed by a change in the membrane potential arecalled voltage-gated channels. The opening and closing of the channel is believed to bedue to the movement of the charged region of the channel back and forth through theelectrical field of the membrane. Voltage-gated channels exist in three states: (1) resting state (the channel is closed but can be activated) (2) active state (the channel is open), and (3) refractory state (the channel is inactivated). Changes in the electrical potential difference across the membrane provide theenergy for gating in these channels. Genes encoding for voltage-gated Na+, K+, and Ca2+channels belong to one family. These channels are described as follows. The voltage-gated Na+ channel is formed by a single long polypeptide (a string ofamino acids containing peptide bonds) that has four domains (I-IV). Each domain hassix hydrophobic alpha helices (S1aS6) that span back and forth within the cellmembrane. The four domains join together and form an aqueous pore of the channel.An additional hydrophobic region connects the S5 and S6 alpha helical segments,
30. forming a pore loop. The presence of this pore loop makes the channel more permeableto Na+ than to K+. The membrane-spanning S4 alpha helical segment is believed to bevoltage sensitive. At the resting membrane potential, the channel pore is closed. The S4segment undergoes a conformational change when the membrane potential changes(e.g., when the neuron is depolarized), the S4 segment is pushed away from the innerside of the membrane, and the channel gate opens, allowing an influx of Na + ions. Thereare some cases where Na+ permeability is blocked. Tetrodotoxin (TTX), a toxin isolatedfrom the ovaries of Japanese puffer fish, binds to the sodium channel on the outside andblocks the sodium permeability pore. Consequently, neurons are not able to generateaction potentials after the application of TTX. These channels are also blocked by localanesthetic drugs (e.g., lidocaine). The basic structure of the voltage-gated Ca2+ channel is similar to that of thevoltage-gated Na+ channel. Ca2+ ions enter the postsynaptic neurons through thesechannels and activate enzymes. Depolarization of presynaptic nerve terminals results inentry of Ca2+ ions into the terminal via these channels. An increase in the levels ofintracellular Ca2+ results in the release of transmitters from presynaptic nerve terminals.Different varieties of voltage-gated K+ channels have been identified, and they servedifferent functions. The general scheme describing the components of this channel issimilar to that of the voltage-gated Na+ channel, except that the voltage-gated K+channel consists of four polypeptides. It should be recalled that each polypeptidecontributing to the formation of a large protein molecule is called a subunit. Eachsubunit of a voltage-gated K+ channel consists of six alpha-helical membrane-spanningsegments (S1 a S6). A pore loop makes the channel more permeable to K + than to Na+.The S4 segment acts as an activation gate. The K+ channels are generally blocked bychemicals such as tetraethylammonium (TEA) or 4-aminopyridine. The ligand-gated channels are opened by noncovalent binding of chemicalsubstances with their receptors on the neuronal membrane. These chemical substancesinclude: (1) transmitters or hormones present in the extracellular fluid that bind to theirreceptors on the extracellular side of the channel and bring about a conformationalchange to open the channel (e.g., acetylcholine, Î³-aminobutyric acid [GABA], orglycine); and (2) an intracellular second messenger (e.g., cyclic adenosine monophosphate,which is activated by a transmitter such as norepinephrine). The second messenger canopen the channel (1) directly by binding to the channel and causing a conformationalchange or (2) indirectly by phosphorylating the channel protein in the presence of aprotein kinase and causing a conformational change; this effect on the channel isreversed by dephosphorylation catalyzed by a protein phosphatase. Genes encoding fortransmitter-gated channels (e.g., channels activated by acetylcholine, GABA, orglycine) and genes encoding for voltage-gated channels belong to different families.Mechanically gated channels open by a mechanical stimulus and include the channelsinvolved in producing generator potentials of stretch and touch receptors.23 – Spreading of membrane potentials. Length and time constant of themembrane. An action potential elicited at any one point on an excitable membrane usuallyexcites adjacent portions of the membrane, resulting in the propagation of the actionpotential.
31. A nerve fiber excited at its midportion-develop increased permeability to Na+.Positive electrical charges carried by the inward diffusing Na+ flow inside the fiberthrought depolarized membrane and then for several milimiters along the core of theaxon. These positive cgarges increase the voltage to above the thereshold. Thus thedepolarization process travels along the entire extent of the fiber and the transmission ofthis depolarization process is called nerve impulse. The action potential will travel inboth directions away from the stimulus until the entire membrane becomes depolarized. Once an action potential has been elicited at any point on the membtrane of anormal fiber, the depolarization process travels over the entire membrane if conditionsare right, or it does not travel at all if conditions are not right- this is called “all ornothing principle”, and it applies to all normal excitable tissues. Occasionally, the actionpotential reaches a point on the membrane at which it does not generate voltage tostimulate the next area of the membrane. When this occurs, the spread of depolarizationstops. Therefore, for continued propagation of an impulse , the ratio of action potentialto threshold for excitation must at all times be greater than 1 – safety factor forpropagation. Length-constant: measures the effectiveness of neuron in longitudinal signaltransduction. Rm λ= √ ------------------- (Ri + Ro ) SOFIA: lambda e igual a raiz quadrada de abrir parentesis Rm sobre abrirparentesis ( Ri + Ro ) Rm: is the resistance across the membrane Ri: resistance inside the membrane Ro: is the resistance outside the membrane The larger the length constant the bigger the effect of the action potential Long leght constant results in spatial summation Time constant: T= Rm . Cm R: resistance C: capacitance Long-time constant results in temporal summation 24 – Temporal summation of membrane potentials. Temporal summation: is an effect generated by a single neuron as a way ofachieving action potential. Summation occurs when the time constant is sufficientlylong and the frequency of rises in potential are high enough that a rise in potential
32. begins before a previous one ends. The amplitude of the previous potential at the pointwhere the second begins will algebraically summate, generating a potential that isoverall lager than the individual potentials. This allows the potential to reach thethereshold to generate the action potential. Thus successive postsynaptic potentials caused by discharges from a single pre-synaptic, if they occur rapidly enough, can summate in the same way that postsynapticpotentials may summate from widely distributed terminals over the surface of a neuron. The degree of temporal summation is directly proportional to time – constant;and it occurs when the second potential arrises before the 1st has decreased. Temporal summation is involved in vision. The inverse proportion of intensityand time, applies as long as the stimulus is no greater than 0.1 second. For example, at0.1 second, 130 quanta are absorbed, un any matter of provision, but when raised to 1second there is a lesser rate of summation, needing 230 quanta to compensate for thedecrease in intensity. The frequency of vision is function of frequency of flashes, so thelonger the stimulus, the better chance it can attain the number of quanta needed forvision. 25 – Conduction velocity of the action potential, its determiants. When a region of an unmyelinated axonal membrane is depolarized sufficientlyby a depolarizing stimulus (e.g., a synaptic potential in a neuron) to reach a threshold
33. potential, voltage-gated Na+ channels open, Na+ flows into the axoplasm, and an actionpotential is generated in that region of the axon. Some of the current generated by theaction potential spreads by electrotonic conduction (passive spread) to an adjacentregion of the axon. The passive spread of current occurs by movement of electrons, andmovement of Na+ ions is not required. At the adjacent region, the passive spread ofcurrent results in opening of voltage-gated Na+ channels, influx of Na+ into theaxoplasm, and generation of an action potential. In other words, the passive spread ofvoltage along the length of an axon results in an active regeneration process. The propagation of an action potential along the axon depends on the cableproperties of the axon. The larger the diameter of the axon, the lower the resistancethere is to the flow of current along its length. Therefore, the conduction velocity(propagation of action potential) along the length of the axon can be increased byincreasing its diameter. For example, the axons of stellate ganglion neurons in the squidare about 1 mm in diameter (1000 times larger than the axons of mammalian neurons).The conduction of action potential in these squid giant axons is faster than inmammalian axons. The squid needs these fast conducting axons for faster contraction ofthe mantle muscles that produce a jet propulsion effect needed for quick escape frompredators. In vertebrates, the conduction velocity is increased by myelination of axon. Amyelin sheath consists of about 1-mm lengths of as many as 300 concentric layers ofmembrane around a single axon. In the peripheral nervous system, myelin is formed bySchwann cells. In the central nervous system, oligodendrocytes form the myelin. Nodesof Ranvier (bare segments of the axonal membrane with a very high density of voltage-gated Na+ channels) are present in between the segments of the myelin sheath. Themyelinated segments of an axon are not excitable and have a high resistance to theleakage of current across them. On the other hand, passive spread of current cangenerate an intense current at the nodes of Ranvier due to the presence of a high densityof voltage-gated Na+ channels.When a depolarizing stimulus (e.g., a synaptic potential in a neuron) arrives at a node ofRanvier, Na+ channels open, there is an influx of Na+ ions, and an action potential isgenerated at that node. Some current generated by the action potential spreads passivelyto the next node of Ranvier, and depolarization of the membrane at this node results inthe generation of an action potential. By this time, Na+ channels at the preceding nodeare inactivated, K+ channels open, and repolarization occurs. Thus, the action potentialpropagates along a myelinated axon by saltatory conduction (i.e., the jumping of anaction potential from one node to another). Myelination of an axon has two advantages:(1) conduction is very rapid along an axon, and (2) there is a conservation of metabolicenergy because excitation is restricted to the nodal regions that are relatively small (0.5Âµm). Conduction is also influenced by temperature, a high temperature leads to ahigher conduction velocity We can also note that the spinocerebellar tract has highest conduction velocity. 26 – Electrical and chemical transmission at synapses. Types of Synaptic Transmission:
34. Two types of synaptic transmission electrical and chemical are recognized in thenervous system. It should be noted that the electrical synapses are relatively lesscommon than the chemical synapses in the mammalian nervous system.Electrical Transmission In electrical transmission between the nerve cells, the current generated by animpulse in one neuron spreads to another neuron through a pathway of low electricalresistance. Electrical synapses occur at gap junctions. In an electrical synapse, ionchannels connect the cytoplasm of the presynaptic and postsynaptic cells. In the adultmammalian central nervous system, electrical synapses are present where the activity ofneighboring neurons needs to be highly synchronized. For example, hormone-secretingneurons in mammalian hypothalamus are connected with electrical synapses so that theyfire almost simultaneously and secrete a burst of hormone into the circulation. At an electrical synapse, the current generated by voltage-gated channels at thepresynaptic neuron flows directly into the postsynaptic neuron. Therefore, transmissionat such a synapse is very rapid (<0.1 msec). At some synapses (e.g., in the giant motorsynapse of crayfish), the current can pass in one direction (from presynaptic topostsynaptic neuron) but not in the reverse direction. Such synapses are called rectifyingor unidirectional synapses. At other synapses, the current can pass equally well in bothdirections. Such synapses are called nonrectifying or bidirectional synapses. Mostelectrical synapses in mammalian nervous system are believed to be the nonrectifyingtype.Chemical Transmission: At chemical synapses, there is no continuity between the cytoplasm of thepresynaptic terminal and postsynaptic neuron. Instead, the cells are separated bysynaptic clefts, which are fluid-filled gaps (20-50 nm). The presynaptic andpostsynaptic membranes adhere to each other due to the presence of a matrix ofextracellular fibrous protein in the synaptic cleft. The presynaptic terminal containssynaptic vesicles that are filled with several thousand molecules of a specific chemicalsubstance, the neurotransmitter. Pyramid-like structures consisting of proteins arise from the intracellular side ofthe presynaptic terminal membrane and project into the cytoplasm of the presynapticterminal. These pyramids and the membranes associated with them are called activezones and are the specialized release sites in the presynaptic terminal. The vesiclescontaining the neurotransmitter are aggregated near the active zones. Mechanisms of Transmitter Release: An action potential depolarizes the presynaptic nerve terminal, voltage-gatedCa channels located in the presynaptic terminal membrane open, Ca2+ permeability 2+increases, and Ca2+ enters the terminal. These events cause the membrane of the27 – Excitatory and inhibitory neurotrasmitters.Neurotrasmitter: chemical substance that is synthesized in a neuron, released at asynapse following depolarization of the nerve terminal (usually dependent on influx of
35. calcium ions), which binds to receptors on the postsynaptic cell and/or presynaptic terminal to elicit a specific response. (1) the substance must be synthesized in the neuron, and the enzymes needed for its synthesis must be present in the neuron;Small Molecule it must be released in sufficient quantity to elicit a response from the (2) GaseousNeurotransmittersneuron or cell located in the effector Neurotransmitters postsynaptic Neuropeptides organ;Acetylcholine(3) mechanisms forOpioid peptides Nitric oxide neurotransmitter from the removal or inactivation of theExcitatory amino acids exist; and Î˛-endorphin, synaptic cleft must Glutamate (4) it should mimic the action of the endogenously released neurotransmitter Methionine- Aspartate administered exogenously at or near a synapse. when enkephalinInhibitory amino acids Leucine-enkephalin GABA Endomorphins Glycine Nociceptin Classes ofBiogenic amines Substance P Neurotrans- Catecholamines mitters Dopamine Norepinephrine Epinephrine Indoleamine In the CNS, a neuron is contantly bombarded by neurotrasmitters, each of which Serotonin (5- can generate or modify a synaptic potential.hydroxytryptamine, [5-HT]) Neurotrasmitters that move the membrane potential towars depolarization with Imidazole amine the resultant production of an action potential are known as excitatory neurotrasmitters. Histamine Neurotrasmitters that move the membrane away from depolarization by making Purines the resting membrane potential more negative, the membrane is hyperrepolariyed, are ATP known as inhibitory neurotrasmitters. Adenosine Because the postsynaptic response is actually elicited by the receptor rather than by the trasmitters, the postsynaptic receptor determines whether a given neurotransmitter will be excitatory or inhibitory. Some neurotrasmitters can have either effect, depending on the type of postsynaptic receptor present. Excitatory: Acetylcholine, glutamate, aspratate.. Inhibitory: Dopamine, adenosine, serotonin, histamine, GABA… Both: Epinepherine, norepinepherine, glycine Acetylcholine Neurotransmitter in both the peripheral nervous system (PNS) and central nervous system (CNS). Acetylcholine is one of many neurotransmitters in the autonomic nervous system (ANS) and the only neurotransmitter used in the somatic nervous system. It is also the neurotransmitter in all autonomic ganglia. In the peripheral nervous system, acetylcholine activates muscles, and is a major neurotransmitter in the autonomic nervous system. When acetylcholine binds to acetylcholine receptors on skeletal muscle fibers, it opens ligand gated sodium channels in the cell membrane. Sodium ions then enter the muscle cell, stimulating muscle contraction. Acetylcholine, while inducing contraction of skeletal muscles, instead
36. induces decreased contraction in cardiac muscle fibers. This distinction is attributed todifferences in receptor structure between skeletal and cardiac fibers. In the autonomic nervous system, acetylcholine is released in the following sites: • all pre- and post-ganglionic parasympathetic neurons • all preganglionic sympathetic neurons o preganglionic sympathetic fibers to suprarenal medulla, the modified sympathetic ganglion; on stimulation by acetylcholine, the suprarenal medulla releases epinephrine and norepinephrine • some postganglionic sympathetic fibers o sudomotor neurons to sweat glands. In the central nervous system, ACh has a variety of effects as aneuromodulator, e.g., for plasticity and excitability. Other effects are arousal andreward. Damage to the cholinergic system in the brain has been suggested to play a rolein the memory deficits associated with Alzheimers Disease.Types of acetylcholine receptors:• Nicotinic AChRs are ionotropic receptors permeable to sodium, potassium, and chloride ions. They are stimulated by nicotine and acetylcholine. They are of two main types, muscle type and neuronal type. The former can be selectively blocked by curare and the latter by hexamethonium. The main location of nicotinic AChRs is on muscle end plates, autonomic ganglia (both sympathetic and parasympathetic), and in the CNS.• Muscarinic receptors are metabotropic, and affect neurons over a longer time frame. They are stimulated by muscarine and acetylcholine, and blocked by atropine. Muscarinic receptors are found in both the central nervous system and the peripheral nervous system, in heart, lungs, upper GI tract and sweat glands. Glutamate: Some of the important physiological and clinical considerations relevant toglutamate are as follows. • Glutamate has been implicated as a transmitter in a variety of circuits in the brain. E.g. excitatory amino acids may be involved in learning and memory processes, as well as motor functions. Dopamine is a neurotransmitter occurring in a wide variety of animals. In thebrain, it functions as a neurotransmitter, activating the five types of dopamine receptors
37. — D1, D2, D3, D4 and D5, and their variants. Dopamine is produced in several areas ofthe brain, including the substantia nigra and the ventral tegmental area. Dopamine isalso a neurohormone released by the hypothalamus. Its main function as a hormone is toinhibit the release of prolactin from the anterior lobe of the pituitary. Epinepherine: when in the bloodstream, it rapidly prepares the body for actionin emergency situations. The hormone boosts the supply of oxygen and glucose to thebrain and muscles, while suppressing other non-emergency bodily processes. Itincreases heart rate and stroke volume, dilates the pupils, and constricts arterioles in theskin and gastrointestinal tract while dilating arterioles in skeletal muscles. It elevates theblood sugar level by increasing catabolism of glycogen to glucose in the liver, and at thesame time begins the breakdown of lipids in fat cells. Like some other stress hormones,epinephrine has a suppressive effect on the immune system. Epinephrines actions are mediated through adrenergic receptors. Epinephrine is anon-selective agonist of all adrenergic receptors. It activates α1, α2, β1, and β2 receptorsto different extents. Specific functions include: • It binds to α1 receptors of liver cells, which activate inositol-phospholipid signaling pathway, signaling the phosphorylation of glycogen synthase and phosphorylase kinase (inactivating and activating them, respectively), leading to the latter activating another enzyme—glycogen phosphorylase—which catalises breakdown of glycogen (glycogenolysis) so as to release glucose to the bloodstream. Simultaneously protein phosphatase-1 (PP1) is inactivated, as in the active state PP1 would reverse all the previous phosphorylations. • Epinephrine also activates β-adrenergic receptors of the liver and muscle cells, thereby activating the adenylate cyclase signaling pathway, which will in turn increase glycogenolysis. β2 receptors are found primarily in skeletal muscle blood vessels where they triggervasodilation. However, α-adrenergic receptors are found in most smooth muscles andsplanchnic vessels, and epinephrine triggers vasoconstriction in those vessels. Epinepherine is found in the spinal cord, hypothalamus, thalamus andperiaqueducts. Serotonin: Serotonin-containing cells in the raphe regions of the brainstem are believed toplay a role in descending pain-control systems. Other serotonin-containing neurons mayplay a role in mediating affective processes such as aggressive behavior and arousal.Serotonin synthesized in the pineal gland serves as a precursor for the synthesis ofmelatonin, which is a neurohormone involved in regulating sleep patterns. Serotonin isalso believed to play an important role in depression. Histamin: Histamine has been implicated as a transmitter in the regulation of food andwater intake, as well as in thermoregulation and autonomic functions.
38. GABA: • GABA is an inhibitory transmitter in many brain circuits. E.g, GABA is used as an inhibitory neurotransmitter by the Purkinje cells in the cerebellum. Alteration of GABAergic circuits has been implicated in neurological and psychiatric disorders like Huntingtons chorea, Parkinsons disease, senile dementi… • Therefore, dietary deficiency of vitamin B6 can lead to diminished GABA synthesis. In a disastrous series of infant deaths.. GABA content in the brain of these infants was reduced. Subsequently, there was a loss of synaptic inhibition that caused seizures and death. • Since epileptic seizures can be facilitated by lack of neuronal inhibition, increase in the inhibitory transmitter, GABA, is helpful in terminating them • Barbiturates act as agonists or modulators on postsynaptic GABA receptors and are used to treat epilepsy.28 – Excitatory and inhibitory postsynaptic potentials. Postsynaptic potentials are changes in the membrane potential of thepostsynaptic terminal of a chemical synapse. Postsynaptic potentials are gradedpotentials, and their function is to initiate or inhibit action potentials. They are causedby the presynaptic neuron releasing neurotransmitters from the terminal button at theend of an axon into the synaptic cleft. The neurotransmitters bind to receptors on thepostsynaptic terminal, which may be a neuron or a muscle cell in the case of aneuromuscular junction. These are collectively referred to as postsynaptic receptors,since they are on the membrane of the postsynaptic cell. Neurotransmitters bind to theirreceptors by having a particular shape or structure, somewhat like the way a key fitsinto certain locks. Postsynaptic potentials are subject to summation, spatially and/or temporally.Excitatory postsynaptic potential (EPSP) is a temporary depolarization ofpostsynaptic membrane potential caused by the flow of positively charged ions into thepostsynaptic cell as a result of opening of ligand-sensitive channels. A postsynapticpotential is defined as excitatory if it makes it easier for the neuron to fire an actionpotential. IPSPs are sometimes caused by an increase in positive charge outflow. Theflow of ions that causes an EPSP is an excitatory postsynaptic current (EPSC). Inhibitory postsynaptic postsynaptic potentials. An inhibitory postsynaptic potential (IPSP) is a synaptic potential thatdecreases the chance that a future action potential will occur in a postsynaptic neuron orα-motoneuron.. They can take place at all chemical synapses which utilize the secretion
39. of neurotransmitters to create cell to cell signaling. Inhibitory presynaptic neuronsrelease neurotransmitters which then bind to the postsynaptic receptors; this induces apostsynaptic conductance change as ion channels open or close. An electrical current isgenerated which changes the postsynaptic membrane potential to create a more negativepostsynaptic potential. Depolarization can also occur due to an IPSP if the reversepotential is between the resting threshold and the action potential threshold. Anotherway to look at inhibitory postsynaptic potentials is that they are also a chlorineconductance change in the neuronal cell because it decreases the driving force. In general, a postsynaptic potential is dependent on the type and combination ofreceptor channel, reverse potential of the postsynaptic potential, action potentialthreshold voltage, ionic permeability of the ion channel, as well as the concentrations ofthe ions in and out of the cell; this determines if it is excitatory or inhibitory. IPSPsalways want to keep the membrane potential more negative than the action potentialthreshold and can be seen as a “transient hyperpolarization” EPSPs and IPSPs competewith each other at numerous synapses of a neuron; this determines whether or not theaction potential at the presynaptic terminal will regenerate at the postsynapticmembrane. Some common neurotransmitters involved in IPSPs are GABA and glycine.29 – Describe structural arrangement of the neuromuscular junction and itsfunction.The neuromuscular junction: The skeletal muscle fibers are innervated by large,myelinated nerve fibers that originate from large motorneurons in the anterior horns ofthe spinal cord. Each nerve fiber, after entering the muscle belly, normally branches andstimulates from three to several hundred several skeletal muscle fibers. Each nereveendings makes a junction, neuromuscular junction, with the muscle fiber near itsmidpoint. The action potential initiated in the muscle fiber by the nerve signal travels inboth directions towards the muscle fiber ends. The nerve fibres forms a complex of branching nerve terminals that invaginateinto the surface os the muscle fiber but lie outside the muscle fiber plasma membrane.The entire structure is called the motor end plate. It is vovered by one or more Scwmanncells that insulate it from the surronfing fluids. In the junction between a single axon terminal and the muscle fiber membrane,the invaginated membrane is called the synaptic gutter or synaptic trough, and the spacebetween the terminal and the fiber membrane is called the synaptic space or synapticcleft. This space is 20 to 30 nanometers wide. At the bottom of the gutter are numeroussmaller folds of the muscle membrane called subneural clefts, which gratly increase thesurface area at which the synaptic transmitter can act. In the axon terminal are many mitochondria that supply ATP, the energy sourcethat is used for the synthesis of an excitatory transmitter acetylcholine. Theacetylcholine in turn excites the muscle fiber membrane. Acetylcholine is synthetized inthe cytoplasm of the terminal, about 300.000 of which are normally in the terminals of asingle end plate. In the synaptic space are large quantities of the enzymeacetylcholinesterase, which destroys acetylcholine a few milliseconds after it has beenreleased from the synaptic vesicles. When a nerve impulse reaches the neuromuscular junction, about 125 vesicles ofacetylcholine are released from the terminals into synaptic space.
40. On the inside surface of the neural membrane are linear dense bars. To each sideof each dense bar are protein particles that penetrate the neural membrane; these arevoltage-gated calcium channels. When an action potential spreads over the terminal,these channels open and allow calcium ions to diffuse from the synaptic space to theinterior of the nerve terminal. The calcium ions, in turn, are believed to exert anattractive influence on the acetylcholine vesicles, drawing them to the neural membraneadjacent to dense bars. The vesicles then fuse with the neural membrane and empty theiracetylcholine into the synaptic space by the process of exocytosis.Myastenia gravis and Lambert-Eaton syndrome. Myastenis gravis is a serious and sometimes fatal disease in which skeletalmuscles are weak. It is caused by the formation of circulatory antibodies to the muscletype of nicotinic acetylcholine receptors. These antibodies destroy some of the receptorsand bind others to neighbouring receptors triggering their removal by endocytosis. Drugs affecting transmission at neuromuscular junction: a) some drugs act on acetylcholine thus stimulating the muscle fiber, e.g. nicotine b) some drugs may block transmission e.g. muscle relaxant. c) some drugs stimulate neuromuscular junction by inactivation ach- acetylcholinesterase e.g. physostigmine30 – Presynaptic inhibition and posttetanic potentiation In addition to the inhibition caused by inhibitory synapses operating at theneuronal membranes which is called post-synaptic inhibition, another type of inhibitionoften ocuurs in the presynaptic terminals before the signals even reaches the synapse –pre-synaptic inhibition. Pre-synaptic inhibition is the phenomenon that occurs when a presynapticneuron exerts inhibitory influences through transmitters at an axo-axonic synapse withthe terminal in a postsynaptic neuron. In presynaptic inhibition, the inhibition is caused by discharge of inhibitorysynapses that lie on the presynaptic terminals nerve fibrils before their endingsterminate on the post-synaptic neuron. In most instances, the inhibitory transmitterreleased is GABA, this has the specific effect of opening ion channels, allowing CL- todiffuse into the terminal fibril. Therefore the action potential itself becomes greatly reduced, thus also reducingthe degree of excitation of the postsynaptic neuron. Presynaptic inhibition occurs in many of the sensory pathways in the nervoussystem. 3 mechanisms of presynaptic inhibition are seen:⇒ Activation of the presynaptic receptors increases Cl- conductance, and this has been shown to decrease the size of the action potentials rwaching the excitatory ending.⇒ This in turn reduces Ca++ entry and consequently the amount of excitatory transmitter released. Voltage-gated K+ channels are also opened and the resulting K+ also decreases Ca++ influx.⇒ Evidence for direct inhibition of transmitter release independent of Ca++ influx into the excitatory ending is evident.
41. Post-tetanic potentiation If we stimulate motor unit and correlate it with the srenght of muscle contraction we can observe the principles of frequency summation and tetanization. First, with a lower rate of stimulation (times per second) and then increasing the frequency there comes a point where each new contraction occurs before the preeciding one is over. As a result, the second contraction is added partially to the first, so that the total strength of contraction rises progressively with increasing frequency. When the frequency reaches a critical level, the successive contractions eventually become so rapid that they fuse together, and the whole muscle contraction appears to be completely smooth and continuos. This is called tetanization. At a slightly higher frequency, the strength of contraction reaches its maximum, so that any additional increase in frequency beyond that point has no further effect in increasing contractile force. This occurs because enough calcium ions are maintained in the muscle sarcoplasm, even between action potentials, so that full contractile state is sustained without allowing any relaxation between the action potentials. The tetanizing stimulation causes Ca++ to accumulate in the presynaptic neuronto such a degree that the intracellular binding sites that keep cytoplasm Ca++ low areoverwhelmed. Postetanic potentiation is opposite to habituation31 – Spontaneously active neurons: Many neurons do not maintain a steady resting potential but fire impulsesspontaneously. Two patterns often seen are: a) regular firing or “beating” b) grouped firing or “bursting” In spontaneously active neurons, resting Na+ conductance is high, the leakagecurrent depolarizes and the threshold is crossed, and an action potential is fired. a) In regular firing neurons: in these neurons the membrane potential is lessnegative due to their possession of high Na+ leak conductance and low K+ leakconductancy. As the membrane potential moves to a more positive value, the theresholdis crossed quickly. After an impulse, voltage K+ channels open and the membrane ishyperepolarized. There is then a return to the resting potential due to to Na+ leakage. b)In bursting neurons: these neurons have the same membrane channels as firing neurons, they regulate action potentials during a burst. In depolarization of an action potential, voltage-gated Ca++ channels are opened to allow Ca++. They are slow, voltage-gated channels allow Na+, Ca++ exchange. This slow depolarization predominate during the impulse generating phase of the burst cycle. K+ channels which are activated by Ca++ are responsible for hyperrepolarisation (calcium-gated K+ channel). In bursting neurons, the leakage is slow, voltage dependent depolarizing channels (Na+, Ca++) generate the burst in a action potential. During this phase, Ca++ enters the cell by the voltage dependent Ca++ channels and activates Ca++
42. gated K+ channels. K + hyperrepolarizes the membrane until the moment when Ca++ is pumped out of the cell or sequestrated.Spontaneous active neurons are important for circuits controlling respiration,locomoytion as well as other activities32 – Coding of sensory information Cells specialized to respond to a specific environmental stimuli are termedsensory receptor cells. a) a neuron specialized for sensory reception b) a receptor cell connected to an afferent neuron c) sense organ composed of receptor cells and additional accessory to transform the stimulus. Receptor cells respond specifically to certain stimuli (receptor specificity) , there are 4 major groups of receptors in mammals: a) thermoreceptors b) chemoreceptors c) photoreceptors d) mechanoreceptors A stimulus is characterized by its modality, intensity, duration and location. Sensation evoked by a stimulus depends on the part of the brain that has been stimulated – Pacinian corpuscle stimulation either by touch or imitation from a tumour produces a touch sensation. Sensory information are processed by the thalamus and is transmitted to thecerebral cortex where the nerve pathways from a particular sense organ are stimulated,the sensation evoked is that for which the receptor is specialized, no matter how longthe pathway or where along the pathway the activity has been initiated. Law of projection: no matter where a particular sensory pathway is stimulatedalong its course to the cortex, the conscious adaptation produced is referred to thelocation of the receptor, (e.g. phantom limb sensation seen in amputated people or inneurosurgical experiments with conscious patients, stimulation of specific part of cortexmay produce tickling sensations)
43. The magnitude of the sensation felt is proportion to the logarithm of the intensityof the stimulus (Weber-Fechner law) : describe the relationship between the physicalmagnitudes of stimuli and the perceived intensity of the stimuli. ∆I ------ = k I∆I= represents the difference thresholdI: represnts the initial stimulus intensityk: constant The intensity discrimination also involves the variation of frequency of actionpotential and varies with the number of receptors activated. Sensation evoked by stimulus depends on the part of the brain that has beenstimulated; e.g: stimulation of touch centres evoke touch sensations The term sensory unit is applied single sensory axon and all its peripheralbranches. The receptor field of a sensory unit is the area from which a stimulusproduces a response in that unit. As strength of stimulus increases, it spreads and coversa large area and activates sense organs and neurons in the surrounding area. 33 – Adaptation of sensory neurons. Sensory receptors convert environmental energy into action potential in neurons.Characteristic of sensory receptors is that they adapt to stimuli over time. There are five types of sensory receptors: a) chemoreceptors – taste, smell, osmolality concentration of CO2 b) mechanoreceptors – touch, pressure c) electromagnetic – light on retina d) nociceptors - pain d) thermoreceptors - temperature A general characteristic of all sensory receptors is that they adapt either partiallyor completely to their stimuli after a period of time. That is when a continuous sensorystimulus is applied, the receptors respond at a high impulse rate at first and then at aprogressively slower rate until finally many of them no longer respond. The pacinian corpuscles adapts extremely rapid and hair receptors adapt within asecond or so, whereas some joint capsule and muscle spindle receptors adapt slowly. Furthermore, some sensory receptors adapt to a far greater extent than others. It isprobable that all the mechanoreceptors adapt completely, but some require hours ordays to do so that’s why they are called “non-adapting” receptors. The longest measured time for complete adaptation of a mechanoreceptor isabout 2 days as for example carotid and baroreceptors.Another way of classifying receptors are:⇒ Telereceptors – distant receivers
44. ⇒ Exteroreceptors – external environment⇒ Interoreceptors – internal environment⇒ Proprioreceptors – information about body position in spaceAdaptation: when a maintained stimulus of constant strength is applied to a receptor,the frequency of the action potentials in its sensory nerve declines over the time(desesitization). Some organs adapt quickly “phasic receptors” e.g.touch whereas somoothers adapt slowly “tonic receptors” e.g. cold, pain, muscle spindlesHow adaptation occurs:Is different for different type of receptors: a) Light receptors: adapt by adjusting the concentration of light sensitivity chemicals b) Pacinian corpuscle: (mechanoreceptors) adapt by: - it has fluid that when compressed on one side fluid is pushed (receptor potential appears on the onset of compression). Then fluid redistributes so that there is even preussure on all sides (resting potential then disappears) - Accomodation – the nerve fiber becomes accommodated to the stimulus by progressive inactivation of Na+ channels. This is slower adaptation34 – Touch – stimuli, receptors and their characteristics. Touch sensation generally results from stimulation of tactile receptors in the skinor in tissues beneath the skin. There are at least six different types of tactile receptorsknown, but many other similar exist.1) Some free nerve endings everywhere in the skin, can detect touch.2) A special type of touch receptor is meissners corpuscles: this receptor consists ofstacks of horizontally flattened epithelial cells enclosed in a connective tissue sheath.One to four myelinated axons enter the capsule, the myelin sheath (in case ofmyelinated axons) terminates, and the axon arborizes among the epithelioid cells.Meissners corpuscles are located beneath the epidermis of the fingers, palm of the hand,plantar surface of the foot, and the toes (glabrous skin). They are low-threshold, rapidlyadapting mechanoreceptors and are sensitive to touch and vibration.3) Merkels Receptors: these receptors are located in the skin below the epidermisespecially on the lips, distal parts of the extremities, and external genital organs(glabrous skin). The receptor consists of a large epithelial cell in the basal layer of theepidermis that is in close contact with an axon. They are low-threshold, slowly adaptingmechanoreceptors, and are sensitive to pressure stimuli.4) Pacinian Corpuscles: these receptors are located deep in the dermis layer of bothhairy and glabrous skin. For example, these receptors are located in the skin of hands,feet, nipples, and mammary glands. They are also found in the walls of the mesenteries,vessel walls, periosteum, and joint capsules. Pacinian corpuscles consist of concentriclamellae of flattened cells that are supported by collagenous tissue. The spaces betweenthe lamellae are filled with fluid. A myelinated nerve enters the corpuscle, the myelinsheath disappears, and a bare nerve terminal occupies the center of the corpuscle. These
45. receptors are low-threshold and rapidly adapting and are sensitive to rapid indentationof the skin caused by vibration of high frequency.5) Ruffinis Corpuscles: these receptors are located in the dermis layer of both hairyand glabrous skin and are widely distributed. They consist of encapsulated bundles ofcollagen fibrils that are connected with similar fibrils of the dermis. The endings of asensory axon ramify within the collagen fibrils. These receptors are low-threshold,slowly adapting, and sensitive to stretching of the skin. They provide information aboutthe magnitude and direction of stretch.6) Expanded type tactile receptor: they are responsible for giving steady-state signalsthat allow to determine continuous touch of objects on the skin. 35 – Temperature sense – stimuli, receptors and their characteristics. Cold and warmth receptors are stimulated by changes of metabolic rates(differences of temperature alters the rate of intracellular chemical reactions) Temperature receptors: ⇒ warm and cold receptors ⇒ found immediately below skin and are organised separated in as areas of spots ⇒ thought to be free nerve endings ⇒ there are 4-10 times more cold receptors than warmth ones Cold receptors: small, Aδ myelinated nerve endings that branches a number oftimes, the tips of which protrude into the bottom surfaces of basal epidermis. Some coldsensations may be transmitted in type C nerve fibers. Respond to temperatures from10-38oC. >15-25 cold points/cm2 in lips >3-5 cold points / cm2 in finger >1 cold point/cm2 in trunk Warmth receptors: ⇒ presumed to be free nerve endings. ⇒ Trasmited by C nerve fibers. ⇒ Stimulatory diameter of 1mmm. ⇒ 3-10 times less than cold receptors.
46. ⇒ Respond to temperatures of 30-45oC Pathway of signal: ⇒ Enters spinal cord ⇒ Travels to tract of Lissauer ⇒ Terminates on dorsal horn ⇒ Signal enters ascending thermal fibers ⇒ Then cross opposite anterolateral sensory tract and terminate in ⇒ 1)reticular area ⇒ 2) ventrobasal complex of thalamus The signals from cold and hot stimulus are carried by small myelinated AÎ´fibers and unmyelinated C fibers. These fibers enter the tract of Lissauer, branch, andthen ascend or descend one to three segments and terminate in the dorsal horn. Theanatomic pathways that mediate temperature sensations are identical to those thatmediate pain sensation. The pathways mediating temperature sensation also mediatecrude touch from naked nerve endings.36 – Visceral sensation – stimuli, receptors and their characteristics. Visceral sensation: It is a part of the autonomic nervous system. Most visceral receptors are suppliedby myelinated and unmyelinated fibres that terminate as free nerve endings.Functionally most of these receptors act at subconscious level through visceral reflexes. The special receptors include: a) osmoreceptors: are sensory receptors found in the hypothalamus and controllfluid balance in the body b)baroreceptors: detect pressure of blood and can increase or decrease thecardiac output according to the specific circumstances. c) chemoreceptores: detect level of CO2 on head by monitoring level of H+ions Receptors for pain and other senssory modalities are similar to those in skin,however there are some differences, e.g. No proprioreception in viscera, fewertemperature and touch receptors, pain receptors are more sparsely distributed (somestimulation still cause severe pain). Pain receptors are free nerve endings. Its distribution include the periosteum,arterial walls, joint surfaces and surfaces of viscera. The stimuli include: Ischemia: causes pain due to the formation of acidic metabolic end products or tissue degenerative products (proteolytic enzymes, bradykinin). Chemical stimuli: damaging substances leak from the GIT to the peritoneal cavity (e.g. Gastric juice leaks through an ulcer and causes digestion)
47. Spasm of a hollow viscus: spasms of gut, gallbladder, bile duct, ureteres causes pain due to mechanical stimulation of pain endings. Pain may also appear as cramps. Overdistension of a hollow organs: overfilling causes strech and consequently causes pain. There are also insensitive viscera which include liver parenchyma and lungalveoli. Sensations from the thorax and abdomen are transmitted by 2 pathways: 1. The visceral pathway: pain is transmitted via pain nerve fibres and the pain is referred to surface areas of the body, often ate a considerable distance from the apinful organ. The fibres are C type, trasmitting slow-pain. 2. Parietal pathway: parietal sensations are conducted directly into the local spinal nerves from the parietal peritoneum, pleura or pericardium and these sensations are usually localized directly over the painful areas.37 – Nociception, pain – stimuli, receptors, physiological significance. Nociceptors are free nerve endings. There are three types of receptors activatedby different noxious stimuli: a) Mechanical nociceptors are activated by mechanical stimuli (e.g., sharppricking). Fiber group AÎ´ b) Thermal and mechano-thermal receptors are activated by stimuli that causeslow, burning pain; Fiver group AÎ´ c) Polymodal receptors are activated by mechanical stimuli as well astemperature (e.g., hot, cold, burning sensation). Fiber group C Pain is mainly a protective mechanism for the body (warming signal), it occursin any tissue being damaged and it causes the individuals to react to remove the painstimulus. There are two types of pain: a) Lateral pain system: - tractus siponothalamicus lateralis - sharp, acute, suddenly felt pain. - felt with a needle, a knife. - not felt in deeper tissues. b) Medial pain systems: - Spinoreticulothalamic tract - Trigemino-reticulo-thalamic pathways - Slow, persistent pain
48. - With diffuse, unpleasant feelings for some time after the injury has occurredAfferents Carrying Pain Sensations: Information regarding fast and acute painsensations is conducted to the CNS by small, myelinated AÎ´ fibers; conduction velocityin these fibers is much faster than that of C fibers. Slow, chronic pain sensation iscarried to the CNS by unmyelinated C fibers. Both types of fibers enter the spinal cordat the apex of the dorsal horn, branch, and then ascend and descend for one to threesegments and then enter the dorsal horn.Anatomical Pathways Mediating Pain Sensa-tions from the Body: the cell bodies ofsensory neurons mediating pain are located in the dorsal root ganglia (first-orderneurons). The nociceptors represent nerve endings of the peripheral axons of thesensory neurons located in the dorsal root ganglia. The central axons (both AÎ´ and Cfibers) of these sensory neurons reach the dorsal horn and branch into ascending anddescending collaterals, forming the dorsolateral tract (fasciculus) of Lissauer. InLissauers tract, these fibers (AÎ´ and C fibers) ascend or descend a few spinal segments,enter the gray matter of the dorsal horn, and synapse on neurons located in laminae Iand II (substantia gelatinosa). Sensory information from laminae I and II is transmittedto second-order neurons located in laminae IV to VI. The second-order neurons inlaminae IV to VI are collectively called the principal sensory nucleus (nucleusproprius).The neospinothalamic tract is the major ascending pathway involved in conveying painsignals to the higher centers; it arises from the nucleus proprius (principal sensory 38 – Proprioreception – stimuli, receptors, their distribution. Proprioreception is the sense of relative positions of neighbouring parts of thebody. Two types of proprioreceptions: 1. Conscious Proprioception: Proprioceptors respond to mechanical forces generated within the body itself. Inconscious proprioception, the receptors located in the joints and joint capsules(proprioceptors) provide sensory information to the cerebral cortex, which, in turn, usesthis information to generate conscious awareness of kinesthesia (i.e., the joint position,direction, and velocity of joint movements). - Receptors: conscious awareness of kinesthesia is believed to dependpredominantly on joint receptors. Receptors located in ligaments and joint capsulesconsist of free nerve endings and encapsulated receptors. The encapsulated jointreceptors are low-threshold mechanoreceptors. Some of them are slowly adapting andprovide information about the static aspect of kinesthesia (i.e., the ability of anindividual to judge the position of a joint without seeing it and without a movement).Other receptors are rapidly adapting and provide information about the dynamic aspectof kinesthesia (i.e., ability of an individual to perceive the movement of a joint and tojudge the direction and velocity of its movement). - Anatomical Pathways: tactile sensation and conscious proprioception aremediated by the dorsal column (dorsal or posterior funiculus)“medial lemniscus system.The cell bodies of sensory neurons that mediate touch and conscious proprioception are
49. located in dorsal root ganglia. The receptors that mediate tactile sensations (Meissners,Merkels, Pacinian, and Ruffini) and conscious proprioception (receptors located in thejoints and joint capsules) are specialized endings of the peripheral process of thesensory neurons located in dorsal root ganglia. The central axons of these sensoryneurons travel in dorsal roots and enter the dorsal (posterior) funiculus of the spinalcord. 2. Nonconscious Proprioception The impulses arising from the proprioceptors mediating this type of sensation(muscle spindles and Golgi tendon organs) are relayed to the cerebellum rather than tothe cerebral cortex. Proprioception mediated by muscle spindles is predominantlyunconscious. These sensations are mediated by the following muscle receptors: musclespindles and Golgi tendon organs.40 – Draw and describe simplified scheme of a neuronal chain of proprioreceptivepathways from the lower extremity.The dorsal (posterior) spinocerebellar tract:• It is located superficially only above the level of L2.• The axons arise from the neurons at the dorsal nucleus of Clarke in lamina VII at the same side.• They pass through the inferior cerebellar peduncle and terminate ipsilaterally in rostral and caidal portions of the vermis.• Since the dorsal nucleus of Clarke is not present caudal to L3, some dorsal root fibres from more caudal segments ascend first in the posterior columns to upper lumbar segments and then terminate upon neurons of the dorsal nucleus.• Impulse related to the cerebellum via the posterior spinocerebellar tract originate in the muscle spindles, Golgi tendon organs and pressure receptors.• Thus, neurons of Clarke´s nucleus receive monosynaptic excitation mainly via group Ia, Ib and II afferent fibres.• In posterior spinocerebellar tract is somatotropically organized both at spinal levels and its cerebellar terminations.• Impulses are utilized in the coordination of posture and movement of individual lim muscle (lower limb)
50. 41 – Draw and describe simplified scheme of a neuronal chain of somatosensorypathways from the skin of the body and extremities. Anterolateral system: • light (crude) skin touch, heat, cold, nociception. • This system shares one major rule with the discriminative touch system: - primary afferents synapse ipsilaterally - secondary afferents synapse then crossPain afferents (temperature as well) enter the cors laterally, due to their small size, andsynapse more or less immediately because they actually can travel one or two segmentsup or down in the cord before synapsind. Lissaure´s tract: is the tract carrying these migrations axons, but they only in thetract for a short time.
51. The dorsal horn is a multi-layered structure. The thin outermost layer is calledthe posterior marginalis layer. The wide part 2nd layer is the substantia gelatinosa andthe layer deep to that is the nucleus proprius. The 2 types of pain fibres enter different layers of the dorsal horn. Aδ fibres en-ter the post-marginalis and the nucleus proprius and synapse in a 2nd set of neurons. The secondary afferents from both layers cross the opposite side of the spinalcord and ascend in the tract called spinothalamic tract. C fibres enter the substantia gelatinosa and synapse, but they do not synapse onsecondary afferents, instead they synapse on interneurons-must carry the signal to thesecondary afferents in either the posterior marginalis or the nucleus proprius. Spinothalamic tract: lies in the ventral horn of the spinal cord, laterally and ven-tral to the gray matter. It is made of 2nd order afferent sensory neurons that originate inlamina I, III, IV and V of the dorsal horn of gray matter. These cross over the contralat-eral side in the anterior commisure and run rostrally. Anterior spinothalamic tract: consists of the ascending axons of the neuronsfrom the opposite side that are located in the lamina: I (apical), II (gelatinous) and V(proprius). The axons cross the middline in the ventral white comissureclose to the cen-tral canal and ascend in the funiculus to the thalamus. The axons of the anteriorspinothalamic tract convey impulses associated with termal and painful sensations.43 – Draw and describe simplified scheme of a neuronal chain of lemniscal systemof the somatosensory pathways, cite their functions. The action potentials generated by tactile and other mechanosensory stimuli aretransmitted to the spinal cord by afferent sensory axons traveling in the peripheralnerves. The neuronal cell bodies that give rise to these first-order axons are located inthe dorsal root ( or sensory) ganglia associated with each segmental spinal nerve. Dorsalroot ganglion cells are also known as first-order neurons because they initiate the sen-sory process. The ganglion cells thus give rise to long peripheral axons that end in thesomatic receptor specializations, and shorter central axons that reach the dorsolateral re-gion of the spinal cord via the dorsal (sensory) roots of each spinal cord segment. Thelarge myelinated fibers that innervate low-threshold mechanoreceptors are derived fromthe largest neurons in these ganglia, whereas the smaller ganglion cells give rise tosmaller afferent nerve fibers that end in the high-threshold nociceptors and thermocep-tors. Depending on whether they belong to the mechanosensory system or to the painand temperature system, the first-order axons carrying information from somatic recep-
52. tors have different patterns of termination in the spinal cord and define distinct somaticsensory pathways within the central nervous system.− The dorsal column–medial lemniscus pathway carries the majority of information from the mechanoreceptors that mediate tactile discrimination and proprioception;− The spinothalamic (anterolateral) pathway mediates pain and temperature sensation. Upon entering the spinal cord, the first-order axons carrying information fromperipheral mechanoreceptors bifurcate into ascending and descending branches, whichin turn send collateral branches to several spinal segments. Some collateral branchespenetrate the dorsal horn of the cord and synapse on neurons located mainly in a regioncalled Rexed’s laminae III–V. These synapses mediate, among other things, segmentalreflexes s or myotatic reflex. The major branch of the incoming axons, however,ascends ipsilaterally through the dorsal columns of the cord, all the way to the lowermedulla, where it terminates by contacting second-order neurons in the gracile andcuneate nuclei. Axons in the dorsal columns are topographically organized such that45 – Describe distribution of the first- and second- order neurons in the trigeminalsystem and cite the modalities. Pain and temperature pathways from receptors in the head and scalp, anterior toa coronal plane through the ears, are the (1) trigeminothalamic and (2)trigeminoreticulothalamic tracts, both of which terminate in nuclei of the thalamus. These fibers convey impulses via the three divisions of the trigeminal nerve(ophthalmic, maxillary, and mandibular) and cranial nerves VII, IX, and X The cell bodies of the first-order fibers (A-delta and C fibers) are located in thetrigeminalganglion (V), the geniculate ganglion (VII), and the superior ganglia (IX andX). The fibers enter the brainstem and descend as the spinal tract of n.V (spinaltrigeminal tract) on the lateral aspect of the lower pons, medulla, and upper two cervicalspinal cord segments. The spinal trigeminal tract is somatotopically organized withfibers from the ophthalmic division most anterior, maxillary in an intermediate position,and mandibular division fibers together with those from nerves VII, IX, and X mostposterior in the sequence; fibers from each of these nerves descend to the C2 level.They terminate in the spinal nucleus of n.V, which is located medial to the tract. Thespinal tract and nucleus of n.V are the brainstem’s counterpart of the posterolateral tract
53. of Lissauer and lamina I and II and deeper laminae of the spinal cord. The spinalnucleus of n.V is a continuous structure that is subdivided into (1) the rostrally locatedpars oralis (nucleus oralis), which receives touch input from the mouth, lip, and nose,(2) the intermediately located pars interpolaris (nucleus interpolaris), which receivespain input from the tooth pulp (dental pain), and (3) the caudally located pars caudalis(nucleus caudalis), which receives pain, temperature, and light touch input from theface, mouth, and tooth pulp. The pars caudalis extends caudally to the C2 level. From cell bodies in the spinal nucleus of n.V, axons of second-order neuronsdecussate through the lower brainstem reticular formation and ascend near the mediallemniscus as the anterior trigeminothalamic tract (anterior trigeminal tract) to terminatein the ventral posteromedial nucleus of the thalamus and in the posterior thalamicregion. Axons of third-order neurons pass from the thalamus through the posterior limbof the internal capsule and corona radiata before terminating in the head region of theprimary and secondary somatosensory cortices (SI and SII). The trigeminothalamic tractis included in the lateral pain system46 – Describe entrance of individual types of the somatosensory fibres to the spinalcord and their connections to the spinal neurons. Dorsal column-medial lemniscal system: is composed of large, myelinated nervefibres that trasmitt signals to the brain at velocities of 30m/sec Anterolateral system: is composed of smaller myelinated fibres that trasmitt sig-nals at velocities ranging from a few meters /sec up to 40m/sec. The sensory input from the periphery to the CNS is highly organized in thespinal cord in order to trasmit information about the modalities to the brain, and to facil-itate rapid execution of the spinal reflexes. All sensory inforrmation enters the spinal cord through the dorsal root and sepa-rate into two divisions: medial and lateral The lateral division has afferents from fine myelinated and unmyelinated, in-cluding senses as nociception (pain) and from viscera and skin. The medial dorsal rootentry zone has afferents from larger myelinated, from muscle spindles and joints andskin. The medial division contains fibres whose original receptors include those inskin, joints and spindles. The fibres are relatively larger diameter than those in the later-
54. al division and carry information about muscle length and tension.They mediate spinalreflexes either throught direct synapsis with motoneuron or through interneurons. Theyalso trasmitt information to the ascending fiber tracts. Dorsal roots that target the localsegment of entry will enter the gray matter through the dorsal horn and synapse with in-terneurons or with motorneurons at the same segmental level. These dorsal horn entryfibers and inetrneurons therefore constitute the central affent arm of the reflex arm. The lateral division, the axons form a bundle of fibres-Lissauer´s tract- Fiberscontains smaller diameter non-myelinated and myelinated axons. Typically trasmitt re-sponses to thermal and painful (nociceptive) stimuli and the viscera.49 – Draw and describe simplified scheme of endogenous analgetic system.There are opiate receptors throught the central nervous system. In the dorsal horn, theyare located on the terminals of the primary afferents, as well as in the cell bodies of thesecondary afferents. Opiate interneurons in the spinal cord receptoes can be activated bydescending projections from the brainstem (especially the raphe nuclei andperiaqueductal grey). This can block pain trasmission at 2 sites:They can prevent the primary afferent from passing on its signal by blockingneurotrasmitter releasThey can inhibit the secondary afferent so it does not send the signal up to thespinothalamic tract.The analgesia system consists of 3 major components:1. Periaqueductal grey of the mesencephalon -periventricular nuclei (areas) of pons - portions of the 3rd and 4th ventriclesThe neurons from these areas send signals to:2. - Raphe magnus nucleus (a thin midline nucleus located in the lower pons and upper medulla)
55. -Nucleus reticularis paragigantocellularis (located laterally in the medulla)From these nuclei, 2nd order signále are trasmitted down the dorsolateral columns in thespinal cord.3. A pain inhibitory complex located in the dorsal horns of the spinal cord. At this point, the analgesia signals can block the pain before it is relayed to the brain.Several transmitter substances are involved in the analgesia system, mainly enkephalinand serotonin. The endings of many fibers derived from periventricular nuclei and from the theperiaqueductal grey areasecrete enkephalin at their endings. The ending of many fibers in the raphe magnus nucleus release enkephalin whenstimulated. Fibers originating in this area send signals to the dorsal horns of the spinalcord ro secrete serotonin at their endings that causes local and neurons to secreteenkephalin as well Enkephalin is believed to cause both presynaptic ans postsynaptic inhibition typeC snd type Aδ pain fibers whose synapse in the dorsal horns.50 – Describe two pathways for the visceral sensation. Most viscera are innervated only by autonomic nerves: it therefore follows thatvisceral pain is conducted along afferent autonomic nerves. This is the true visceralpathway. The true visceral pathway is transmitted via sensory fibers, both sympatheicand parasympathetic. The sensations are referred to surface areas of the body often farfrom the painful organ, i.e the areas of skin that are innervated by the same segments ofthe spinal cord are the painful viscus. The pain is diffuse and poorly localized. According to the generally accepted theory of referred pain, the brain falselyinterprets the source of noxious stimulation because visceral and somatic nociceptorshave the same spinothalamic neurons in common. Viscerosensory fibers in the sympathetic system, the 1st order neurons, areplaced in the dorsal ganglia. May pass through paravertebral ganglia without synapsing,then, enter spinal nerves through white and grey rami communications. Follows dorsalroot ganglia and lateral horn. Visceral sensation in sympathetic system: ⇒ Pathway from thoracic and abdominal cavity. ⇒ Fibres go to dorsal root ganglion ganglion into dorsal horn, then cross over to opposite side and enter spinothalamic tract and spinoreticular tract. Visceral sensation in parasympathetic system: ⇒ Oropharyngeal mucosa terminates in solitary nucleus
56. ⇒ Carotid sinus (baroreceptor) terminates in solitary nucleus ⇒ Carotid sinua (chemoreceptor) terminates in solitary nucleus51 – Taste – stimuli, receptor cells, trasnduction mechanisms. Stimulus: Sensory receptors in this system are stimulated by chemical molecules. Basicsensations of taste include sweet, bitter, salty, and sour. The areas of the tongue mostsensitive to different taste sensations are: tip of the tongue for sweetness, back of thetongue for bitterness, and sides of the tongue for saltiness and sourness Receptors: The receptor cells that mediate the sensation of taste are located in taste buds,which are the sensory organs for the taste system. Taste buds are located in differenttypes of papillae: filiform, fungiform, foliate, and circumvallate papillae. The filiformand fungiform papillae are scattered throughout the surface of the anterior two thirds ofthe tongue, especially along the lateral margins and the tip. The foliate papillae arepresent on the dorsolateral part of the posterior part of the tongue. The circumvallatepapillae are larger than other papillae and are located in a V-shaped line, which dividesthe tongue into two portions: the anterior two thirds and posterior one third. The tastebuds are located in the lateral margins of the papillae that are surrounded by a deepfurrow bathed by fluids in the oral cavity. Each taste bud has a pore at its tip through which fluids containing chemicalsubstances enter. The taste receptor cells live for about 10 days and have to be replaced. Afferent nerve terminals make contact with the base of the taste receptor cells.
57. The cell bodies of these afferent terminals are located in the ganglia of CN VII (facial),IX (glossopharyngeal), and X (vagus). Transduction mechanisms: The salivary fluids containing chemical substances enter the taste buds throughthe pore at the top and bathe the microvilli, which are located at the tip of the tastereceptor cells. Interaction of the chemical molecule with the specific sites in themembrane of the microvilli brings about the depolarization of the receptor cell toproduce a generator potential. This initial step of depolarization is brought about byopening or closing of different channels: salty taste is mediated by generation of a + +receptor potential due to influx of Na through the amiloride-sensitive Na channell.Sour taste, elicited by acids, is mediated by depolarization of the receptor cell due to +closure of voltage-dependent K channels. Other mechanisms for mediation of tastesensation involve activation of a G-protein that, in turn, activates a cascade of eventsresulting in transmitter release. Substances that generate the sense of sweet flavor (e.g.,sugars) act on receptors that are coupled with Gs-proteins. Activation of G-proteinsresults in activation of adenylate cyclase (adenylyl cyclase), which increases the levelsof cAMP. cAMP activates a phosphokinase that depolarizes the receptor cells by +closing K channels. Bitter substances activate a G-protein, which, in turn, activates 2+phospholipase C and generates the IP3 second-messenger system. IP3 releases Cafrom intracellular stores.52 – Describe taste buds and their sensory innervation. The receptor cells that mediate the sensation of taste are located in taste buds,which are the sensory organs for the taste system. Taste buds are located in differenttypes of papillae: filiform, fungiform, foliate, and circumvallate papillae. The filiformand fungiform papillae are scattered throughout the surface of the anterior two thirds ofthe tongue, especially along the lateral margins and the tip. The foliate papillae arepresent on the dorsolateral part of the posterior part of the tongue. The circumvallatepapillae are larger than other papillae and are located in a V-shaped line, which dividesthe tongue into two portions: the anterior two thirds and posterior one third. The tastebuds are located in the lateral margins of the papillae that are surrounded by a deepfurrow bathed by fluids in the oral cavity. Each taste bud has a pore at its tip through which fluids containing chemicalsubstances enter. The taste bud contains taste receptor cells in different stages ofdevelopment. The taste receptor cells live for about 10 days and have to be replaced.Small cells at the base of the taste bud (basal cells) divide to replace the taste receptorcells. Afferent nerve terminals make contact with the base of the taste receptor cells.The cell bodies of these afferent terminals are located in the ganglia of CN VII (facial),IX (glossopharyngeal), and X (vagus). Central Pathways The taste buds on the anterior two thirds of the tongue are innervated by thefacial nerve (CN VII); taste buds on the posterior one third of the tongue are innervatedby the glossopharyngeal nerve (CN IX); and the taste buds on the epiglottis and
58. pharyngeal walls are innervated by the vagus nerve (CN X). The afferent terminals ofthe facial nerve carry sweet, sour, and salty sensations; while those of theglossopharyngeal nerve carry sour and bitter sensations. Unipolar neurons mediate the sensation of taste. The unipolar neurons mediatingthe sensation of taste via the facial nerve (CN VII) are located in the geniculateganglion, which is situated in the petrous portion of the temporal bone. The peripheralprocesses of these neurons travel in the facial nerve, which exits the cranium at thestylomastoid foramen. At this level, the peripheral processes of the sensory neurons exitfrom the facial nerve and form the chorda tympani nerve, which crosses the cavity ofthe middle ear (horizontally along the in-ner surface of the tympanum and over themanu-brium of the malleus ossicle). The chorda tympani finally joins the lingual branchof the trigeminal nerve and innervates the taste buds on the anterior two thirds of thetongue. The central processes of sensory neurons in the geniculate ganglion travel in theintermediate nerve (adjacent to the facial nerve), enter the solitary tract, and terminate inthe rostral portion (gustatory region) of the solitary nucleus. The unipolar neurons mediating the sensation of taste via the glossopharyngealnerve (CN IX) are located in the inferior (petrosal) ganglion, which is located in thejugular foramen. The peripheral processes of these neurons travel in theglossopharyngeal nerve and finally innervate the taste buds on the posterior one third ofthe tongue. The central processes of sensory neurons in the petrosal ganglion travel inthe glossopharyngeal nerve, enter the solitary tract, and also terminate in the rostralportion of the solitary nucleus, which is known as the gustatory nucleus. The unipolar neurons mediating the sensation of taste via the vagus nerve (CNX) are located in the inferior (nodose) ganglion, which is located just below the jugularforamen54 – Smell – stimuli, receptor cells, tranduction mechanism. Stimulus: Chemicals that generate odors stimulate specialized receptors of the olfactorysystem. Human beings can detect these odors at very low concentrations (a few partsper trillion); thousands of such chemicals can be distinguished. Receptors: The bipolar olfactory sensory (receptor) along with their processes, are presentin the specialized olfactory mucosa of the nasal cavity just below a thin sheet of bonecalled the cribriform plate of the ethmoid bone of the skull. The olfactory sensoryneurons have single dendrites on one end that terminate in the surface of the olfactorymucosa as expanded olfactory knobs. A single unmyelinated axon arises on the oppositeend of the sensory neuron. Collectively, these axons are called the olfactory nerve(cranial nerve [CN] I). The axons of olfactory sensory neurons do not form a singlenerve as in other cranial nerves. Instead, small clusters of these axons penetrate thecribriform plate and synapse in the ipsilateral olfactory bulb. Supporting (sustentacular)cells present in the olfactory epithelium help in detoxifying chemicals that come incontact with the olfactory epithelium. Transduction mechanisms: A protein, called olfactory binding protein, is secreted by the Bowmans glands,which are located in the olfactory mucosa, and is more abundant around the cilia of the
59. olfactory sensory neurons. Although the exact function of the olfactory binding proteinis not known, it is believed that it carries and/or concentrates the odorant (a substancethat stimulates olfactory receptors) around the cilia. At least two second-messengersystems cyclic adenosine monophosphate (cAMP) and inositol triphosphate (IP3) areinvolved in the transduction of olfactory signals. When an odorant molecule binds to thereceptor protein on the cilia, a receptor-odorant complex is formed, which activates a Gprotein. The activated G protein (Golf) combines with guanosine triphosphate (GTP),displacing guanosine diphosphate (GDP). The GTP-Golf complex activates adenylate + 2+cyclase, leading to the generation of cAMP, which, in turn, opens Na /Ca channels. + 2+The influx of Na and Ca results in depolarizing generator potential in the cilia. Inanother pathway, the GTP-Golf complex activates phospholipase C, which generates 2+IP3. IP3 activates and opens Ca channels, causing depolarizing generator potentials. In 2+both second-messenger pathways, an increase in intracellular Ca concentration results 2+ -in the opening of Ca -gated Cl channels, efflux of chloride ions, and furtherdepolarization of the cilia. This depolarization is conducted passively from the cilia tothe axon hillock of the olfactory sensory neuron. When the axon hillock reaches athreshold, action potentials are generated, which are conducted along the axons of theolfactory sensory neurons. These signals are processed in the central olfactory pathwaysfor the sense of smell.55 – Draw and describe simplified scheme of neuronal connections in the olfactorybulb. Olfactory bulb: In the olfactory bulb, the axons of the receptors contact the primary dendrites ofthe mitral cells and tufted cells to form the complex globular synapses – olfactoryglomeruli. The tufted cells are smaller than the mitral cells and have thinner axons, but bothtypes send axons into the olfactory cortex; they appear to be similar from a functionalpoint of view. In addition to mitral and tufted cells, the olfactory bulb contain periglomerularcells (neurons) which are inhibitory neurons connecting one glomerulus to another. Granule cells which have no axons make reciprocal synapses with the lateraldendrites of the mitral and tufted cells. At these synapses, the mitral and tufted cells ex-cites the granule cells by releasing glutamate, and the granule cell side of the synapse inturn inhibits the mitral or tufted cells by releasing GABA.
60. The granular layer also receives input from the raphe nuclei, locus ceuleus andthe diangand band. 56 – Draw and describe simplified scheme of a neuronal chain of pathwayfor conscious sense of smell. Many brain tructures receive olfactory connections. The output axons of the ol-factory bulbs course through the olfactory tract and project directly to several targets.Among the most important targets are the primitive region of the cerebral cortex – ol-factory cortex and some of its neighbouring structures in the temporal lobe. This anato-my makes olfaction unique. All other sensory systems 1st pass through the thalamus be-fore projecting to the cerebral cortex. The olfactory y arrangement produces an unusually direct and widespread influ-ence on the parts of the forebrain that have roles in: odor discrimination, emotion, moti-vation, certain kinds of memory. The conscious perception of smell may be mediated by a path from the olfactorytubercle, to the medial dorsal nucleus of the thalamus to the orbitofrontal cortex. The olfactory tract consists mainly of fibres of the: - anterior olfactory nucleus
61. - lateral olfactory tract - anterior limb of the anterior comissure The lateral olfactory tract which transmits olfactory inputs to the brain, gives offcollaterals to: - limbic system - olfactory cortex - the anterior olfactory nucleusThe axons of the lateral olfactory tract travel caudally as the lateal olfactory stria. Thissynapse in the piriform cortex - a major component of the olfactory cortex and the ol-factory tubercle. The lateral olfactory tract projects futher caudally to the: -anterior cortical amygdaloid nucleus -lateral entorrhinal cortex -periamygdaloid cortex Olfactory cortex: - anterior cortical amygdaloid nucleus - anterior olfactory nucleus - lateral entorrhinal cortex - periamygdaloid nucleus - piriform cortex - olfactory tubercle57 – Describe optical system of the eye The receptor organ for the visual system is the eye. Three layers of tissue enclose the eye: 1. Outermost layer is called the sclera and consists of a tough white fibroustissue. An anterior portion of the sclera, the cornea, is transparent and permits light raysto enter the eye. 2. The middle layer, the choroid, is highly vascularized. It is continuous with theiris and the ciliary body. The iris is the colored portion of the eye that is visible throughthe cornea. The iris has a central opening, which is called the pupil. The size of thepupil is neurally controlled via the circular and radial muscles of the iris. 3. The innermost layer of the eye is the retina. The optic nerve exits the retina at a pale circular region called the optic disc oroptic nerve head. Blood vessels supplying the eye enter via the optic disc. Because there
62. are no photoreceptors in the optic disc, it is called the blind spot. Near the lateral edgeof the optic disc lies a circular portion that appears yellowish in appropriate illuminationdue to the presence of a yellow pigment in the cells located in this region. This region ofthe retina is called the macula lutea. This part of the retina is for central vision. At thecenter of the macula lies a depression called the fovea, which contains primarily cones.The layers of cell bodies and processes that overlie the photoreceptors in other regionsof the retina are displaced in the fovea. A small region at the center of the fovea, knownas the foveola, is also devoid of blood vessels. The fovea, including the foveola,represents the region of retina with highest visual acuity because there is minimumscattering of light rays due to the absence of layers of cells and their processes andblood vessels in this region. Different tissue layers enclosing the eye are continuous with certain structures ofthe eye. For example, sclera is continuous with the cornea, choroid is continuous withthe iris and ciliary body, neural retina is continuous with ora serrata, and nonneuralretina is continuous with epithelium of the ciliary body. Ora serrata is the serratedmargin located just behind the ciliary body and represents the limits of the neural retina(photoreceptors and other cells associated with sensing and processing of lightstimulus).58 – Photopic and scotopic vision. Photopic vision: is the vision of the eye under well-lit conditions. In humansand many animals, photopic vision allows color perception, mediated by cone cells. Thehuman eye uses three types of cones to sense light in three respective bands of color.The biological pigments of the cones have maximum absorption values at wavelengthsof about 420 nm (blue), 534 nm (Bluish-Green), resp. 564 nm (Yellowish-Green). Theirsensitivity ranges overlap to provide vision throughout the visible spectrum. Themaximum efficacy is 683 lumens/W at a wavelength of 555 nm (green). Scotopic vision: is the monochromatic vision of the eye in low light. Since conecells are nonfunctional in low light, scotopic vision is produced exclusively through rodcells so therefore there is no color perception. Scotopic vision occurs at luminancelevels of 10-2 to 10-6 cd/m². Mesopic vision occurs in intermediate lighting conditions (luminance level 10-2to 1 cd/m²) and is effectively a combination of scotopic and photopic vision. Thishowever gives inaccurate visual acuity and colour discrimination.
63. In normal light (luminance level 1 to 106 cd/m²), the vision of cone cells dominates andis photopic vision. There is good visual acuity (VA) and colour discrimination.59 – Photoreceptors – their function and retinal distribution. The Photoreceptors The human retina consists of two types of photoreceptors: the rods and cones.The rods and cones consist of the following functional regions: an outer segment, aninner segment, and a synaptic terminal. The outer segment is located toward the outersurface of the retina and is involved in phototransduction. This segment consists of astack of membranous discs that contain light-absorbing photopigments. These discs areformed by an infolding of the plasma membrane. In the rods, these discs are freefloating because they pinch off from the plasma membrane. In the cones, the discsremain attached to the plasma membrane. The outer segments are constantly beingrenewed. The discarded tips are removed by phagocytosis by pigment epithelial cells.The inner segment contains the nucleus and most of the biosynthetic mechanisms. Theinner segment is connected to the outer segment by a stalk or cilium that containsmicrotubules. The synaptic terminal makes synaptic contact with the other cells. Cones
64. Cones are responsible for daylight vision. The loss of cones results in blindness.Vision mediated by cones is of higher acuity than that mediated by rods. Cones mediatecolor vision, whereas rods do not. Cones have a fast response, and their in-tegrationtime is short. They are concentrated in the fovea. Rods Rods are highly sensitive and can detect dim light. They are specialized for nightvision and saturate in daylight. The loss of rods results in night blindness and loss ofperipheral vision. They contain more photosensitive pigment than the cones. Thephotosensitive pigment is responsible for the ability of rods to capture more light. Both rods and cones, unlike ganglion cells, do not respond to light with an actionpotential. Instead, they respond with graded changes in membrane potential. Theresponse of rods is slow, whereas the response of cones is fast.60 – Transduction of light in photoreceptors.Phototransduction In the outer segment membrane of the photoreceptors (rods and cones), there are +cyclic guanosine monophosphate (cGMP)gated Na channels. cGMP binds directly to +the cytoplasmic side of the channel, which causes it to open, allowing an influx of Na .During darkness, the presence of high levels of cGMP in photoreceptors results in + +opening of Na channels, and an inward current carried by Na flows into the outersegment of the photoreceptor. Thus, the photoreceptors remain depolarized during +darkness. K flows out across the inner segment of the receptor membrane through + + +nongated K (leakage) channels. Steady intracellular concentrations of Na and K are + +maintained by Na -K pumps located in the inner segments of the photoreceptor. A photoreceptor pigment, rhodopsin, is present in the rods. It consists of aprotein called opsin that is attached with a light-absorbing component, called retinal (analdehyde form of vitamin A). Opsin is embedded in the disc membrane and does not
65. absorb light. In the cones, the protein is called cone-opsin, and it is attached with alight-absorbing component similar to that present in rhodopsin. The events that occur in the presence of light: 1. the retinal component of rhodopsin absorbs light, which results in a change in the conformation of the photoreceptor pigment, and a G-protein (called transducin in rods) is stimulated, 2. the G-protein activates cGMP phosphodiesterase (PDE), 3. the activated PDE hydrolyzes cGMP and reduces its concentration, 4. a reduction in the concentration of cGMP results in closing of the cGMP-gated + Na channels, and + 5. the influx of Na is reduced, and the photoreceptor cell is hyperpolarized. Thus, photoreceptors produce a hyperpolarizing generator (receptor) potential instead of a depolarizing generator potential, which is observed in other receptors. The photoreceptors (rods and cones) do not fire action potentials. The rods and cones make synaptic contacts with the dendrites of bipolar andhorizontal cells. The signals from rods and cones are transmitted to the bipolar andhorizontal cells via chemical synapses. As mentioned earlier, vision during normaldaylight depends on cones, while night-vision involves rods.61 – Draw and describe simplified scheme of the connection among retinalneurons.1. Photoreceptors: Rods and cones:- transmit signals to the outer plexiform plexus.- in the outer plexiform layer they synapse with bipolar and horizontal cells.2. Horizontal cells:- which transmit signals horizontally in the outer plexiform layer from the rods andcones.3. Bipolar cells:
66. - which transmit signals vertically from the rods, cones and horizontal cells to the innerplexiform layer-where they synapse with ganglion cells and amacrine cells.4. Amacrine cells:- which transmit signals in two directions, either directly from bipolar cells to ganglioncells or horizontally within the inner plexiform layer from axons of the bipolar cells todendrites of the ganglion cell or to other amacrine cells.5. Ganglion cells:- which transmit output signals from the retina through the optic nerve into the brain62 – Information processing in retina. The cell bodies of bipolar neurons are located in the inner nuclear layer of theretina. These cells constitute the main link in the transmission of visual signals fromrods and cones to ganglion cells. The receptive field of a bipolar cell is a circular area ofthe retina that, when stimulated by a light stimulus, changes the membrane potential ofthe bipolar cell. The receptive field of a bipolar cell consists of two parts: the receptivefield center, which provides a direct input from the photoreceptors to the bipolar cells,and the receptive field surround, which provides an indirect input from thephotoreceptors to the bipolar cells via horizontal cells. The changes in membranepotential of bipolar cells to a light stimulus upon the receptive field center and surroundare opposite. The mechanism of membrane potential changes in the bipolar cells inresponse to light can be summarized as follows: There are two populations of bipolar cells: on-center bipolar cells and off-centerbipolar cells. When stimulated, bipolar cells exhibit graded potentials rather than actionpotentials . Each photoreceptor cell (e.g., a cone) synapses on an on-center and an off-center bipolar cell. Each on-center bipolar cell, in turn, synapses with an on-center
67. ganglion cell (Fig. 16-4B, 4), and each off-center bipolar cell synapses with an off-center ganglion cell. When the receptive field center is in dark, the photoreceptors are depolarized,and they release glutamate constantly. Glutamate released from the photoreceptor +terminals stimulates metabotropic glutamate receptors on the on-center bipolar cells, K +channels are opened, there is an efflux of K , the on-center bipolar cell ishyperpolarized, and the release of its transmitter (glutamate) is decreased. On the otherhand, glutamate released from the photoreceptor terminals stimulates ionotropic + +glutamate receptors on the off-center bipolar cells, Na channels are opened, Na flowsinto the cell, the off-center bipolar cell is depolarized, and the release of its transmitter(glutamate) is increased. Hyperpolarization of on-center bipolar cells results in adecrease in the release of their transmitter, which, in turn, results in a decrease in thefiring of the corresponding on-center ganglion cells. Depolarization of off-center bipolarcells results in an increase in the release of their transmitter which, in turn, results in anincrease in the firing of the corresponding off-center ganglion cells. When the photoreceptor in the receptive field center receives a light stimulus, itis hyperpolarized, and glutamate release from its terminals is decreased. The reductionin the release of glutamate from the photoreceptor terminals causes depolarization of theon-center bipolar cell and an increase in its transmitter release, whereas the off-centerbipolar cell is hyperpolarized, and there is a decrease in its transmitter release.Depolarization of on-center bipolar cells results in an increase in the release of theirtransmitter, which, in turn, results in an increase in the firing of the corresponding on-center ganglion cells. Hyperpolarization of off-center bipolar cells results in a decreasein the release of their transmitter, which, in turn, results in a decrease in the firing of thecorresponding off-center ganglion cells.63 – Describe receptive fields of retinal ganglion cells. Visual and Retinal Fields The visual field of each eye is the region of space that the eye can see lookingstraight ahead without movement of the head. The fovea of each retina is aligned with apoint, called the fixation point, in the visual field. A vertical line can divide the visualfield of each eye into two halves: the left half field and right half field. A horizontal linecan divide each visual hemifield into superior and inferior halves. Each half can befurther divided into quadrants. The vertical and horizontal lines dividing the visual fieldof each eye intersect at the fixation point. Similarly, the surface of the retina may bedivided into two halves by a vertical line drawn through the center of the fovea: a nasalhemiretina that lies medial to the fovea and a temporal hemiretina that is located lateralto the fovea. A horizontal line drawn through the center of the fovea can divide theretina into superior and inferior halves. The vertical and horizontal lines dividing theretina intersect at the center of the fovea. Each hemiretina is further subdivided intoquadrants.
68. The images of objects in the visual field are right-left reversed and inverted onthe retina. Accordingly, images present in the left half of the visual field of the left eyefall on the nasal hemiretina of the left eye, and images present in the right half of thevisual field of the left eye fall on the temporal hemiretina of the left eye. Similarly,images present in the left half of the visual field of the right eye fall on the temporalhemiretina of the right eye, and images present in the right half of the visual field of theright eye fall on the nasal hemiretina of the right eye. A similar relationship existsbetween the superior and inferior halves of the visual fields of the superior and inferiorhemiretinae of each eye. The central portion of the visual field of each eye can be seen by both retinae.This portion of full visual field is called a binocular visual field. The visual fields of thetwo eyes are superimposed; the left half of the binocular visual field represents the lefthalf of the visual field of each eye, and the right half of the binocular visual fieldrepresents the right half of the visual field of each eye. 64 – Draw and describe simplified scheme of a neuronal chain of parallelpathways that convey visual information to the cortex. The left half of the brain controls the right side of the body, and vice versa.Fibers from the nasal retinas cross over at the optic chiasma. Temporal retinas, alreadypositioned do see the opposite side of the world, do not cross. Once the ganglion cell axons leave the retina, they travel through the optic nerveto the optic chiasma, the fibers are called optic tract, it wraps around the cerebral pedun-cles of the midbran to get to the lateral geniculate nucleus (LGN).Lateral geniculate nucleus (LGN):- this is a 6-layered, dome-shaped nucleus in which the optic fiber terminate in a preciseretinotopic pattern.
69. - however, each layer receives input from only one eye: - layers 1,4,6: from the contralateral eye - layers 2,3,5 from the ipsilateral eye- layers 3 to 6 contain small neurons that receive their inputs from the numerical domi-nant class of small ganglion cells sensitive to color and form (Parvocellular layers)- layers 1 and 2 contain larger neurons that receive their inputs from a separate class oflarger ganglion cells that are more sensitive to movement and contrast (Magnocellularlayers)- the neurons in the lateral geniculate nucleus send their axons directly to primary visualcortex, striate cortex, area 17.Visual fibers also pass to several other areas of the brain:1. From the optic tracts to suprachiasmatic nucleus of the hypothalamus (probably docontrol circardian rhytm).2. Into the pretectal nuclei in the midbrain ( to elicit reflex movements of the eyes tofocus an object of importance and to activate the pupillry light reflex.3. Into the superior colliculus to control rapid directional movements of the eyes.4. Vental geniculate nucleus of the thalamus. 65 – Visual cortex, its division and individual contributions to analysis ofthe visual information. Visual Cortex: is located mainly in the occipital lobes. The cortex is dividedinto a primary and secondary visual cortex. The primary visual cortex (V1; Brodmanns area 17) is located on the superiorand inferior banks of the calcarine sulcus on the medial side of the occipital lobe andreceives projections from the lateral geniculate nucleus of the thalamus. This area is thetermination of direct visual signals from the eyes. The secondary visual cortex (V2; Brodmanns area 18) and tertiary visualcortex (V3 and V5; Brodmanns area 19) are located adjacent to the primary visualcortex. The secondary and tertiary visual areas are also known as association,extrastriate, or prestriate areas. Visual area V4 is located in the inferior occipitotemporalarea. V3 is associated with form, V4 is associated with color, and V5 is associated withmotion. The portion of area V5 that is concerned with motion of an object lies in themiddle temporal gyrus. The primary visual cortex sends projections to the secondary visual cortex; fromhere, this information is relayed to the tertiary visual cortex. Thus, information from thenasal retina of the left eye and temporal retina of the right eye (representing the left
70. visual field of both eyes) is directed to the right visual cortex. Likewise, informationfrom the nasal retina of the right eye and temporal retina of the left eye (representing theright visual field of both eyes) is directed to the left visual cortex. The overallrepresentation of the retina in the primary visual cortex is as follows: the macular part ofthe retina is represented in the posterior part of the visual cortex, the peripheral part ofthe retina is represented in the anterior part of the visual cortex, the superior half of theretina relating to the inferior visual fields is represented in the superior visual cortex,and the inferior half of the retina relating to the superior visual fields is represented inthe inferior part of the visual cortex. A total lesion of the visual cortex (or a lesion affecting all of the geniculocorticalfibers) on one side of the brain will produce a contralateral homonymous hemianopsia(i.e., loss of vision of the same half of the visual fields of both eyes). A lesion restrictedto the inferior bank of the calcarine sulcus will cause an upper quadrantanopia. If thelesion affects the left side of the brain, then a right upper quadrantanopia will result. Ifthe lesion involves the upper bank of the calcarine sulcus, then a lower quadrantanopia(i.e., loss of vision of one quarter of the visual field of both eyes) will result. Lesions in the secondary visual areas can produce a variety of deficits, includingvisual agnosia (i.e., failure to understand the meaning or use of an object) and coloragnosia (i.e., inability to associate colors with objects and inability to name ordistinguish colors).67 – Mechanisms of color vision. Color Vision There are three types of cone receptors, each of which contains a differentphotopigment that is sensitive to one of the primary colors (red 700nm, blue 450nm,and green 500nm). The relative frequency of impulses from each cone determines thesensation of any particular color. Besides cones, other cells in the retina that areinvolved in the processing of color vision include the horizontal cells (which are eitherhyperpolarized or depolarized by monochromatic colors) and ganglion cells (which areeither turned on or off by monochromatic colors). Information following stimulation ofa particular cone preferentially by a monochromatic color (e.g., green) is processed bythe visual cortex and interpreted as a particular color (green in this case). If twodifferent types of cones are stimulated equally by two different monochromatic colors(e.g., red and green), the visual cortex interprets them as a yellow color. The visualcortex contains cells that can differentiate between brightness and contrast and cells thatrespond to a particular monochromatic color. Processing of color vision in the visualcortex involves integration of the responses of the cones, horizontal cells, ganglioncells, and lateral geniculate body cells.
71. 68 – Monocular and binocular cues of depth vision. Monocular vision: is vision in which each eye is used separately. By using theeyes in this way, as opposed by binocular vision, the field of view is increased, whiledepth perception is limited. The eyes are usually positioned on opposite sides of theanimals head giving them the ability to see two objects at once. Most birds and lizards(except chameleons) have monocular vision. Owls and other birds of prey are notableexceptions. Also many prey have monocular vision to see predators. Monopsia: is a medical condition in humans who cannot perceive three-dimensionally even though their two eyes are medically normal, healthy, and spacedapart in a normal way. Vision that perceives three-dimensional depth requires more thanparallax. In addition, the resolution of the two disparate images, though highly similar,must be simultaneous, subconscious, and complete. ( If one knows that a person whom one is viewing is 180cm tall, one candetermine how far the person is away, simply by the seeing of the person´s image onones retina. One does not conciosly think about the size but one´s brain has learnt tocalculate the distance of objects when the dimensions are known). Binocular vision: having two eyes confers at least four advantages over havingone.
72. 1. it gives a creature a spare eye in case one is damaged. 2. it gives a wider field of view, e.g, a human has a horizontal field of view of approximately 200 degrees with two eyes but only 160 degrees with one. 3. it gives binocular summation in which the ability to detect faint objects is enhanced. 4. it can give stereopsis in which parallax provided by the two eyes different positions on the head give precise depth perception. Such binocular vision is usually accompanied by singleness of vision orbinocular fusion, in which a single image is seen despite each eyes having its ownimage of any object. Other phenomena of binocular vision include utroculardiscrimination, eye dominance, allelotropia, and binocular rivalry. Binocular summation means that the detection threshold for a stimulus is lowerwith two eyes than with one. There are two forms: First, when trying to detect a faint signal, there is a statistical advantage of usingtwo detectors over using one. Mathematically, the advantage is equal to the square rootof 2, about 1.41. Second, when some cells in the visual cortex receive input from both eyessimultaneously, they show binocular facilitation, a greater level of activity than the sumof the two activities evoked separately from each eye. Stereopsis is an ability to make fine depth discriminations from parallaxprovided by the two eyes different positions on the head. There are two sorts:quantitative stereopsis, in which the depth seen is very similar to the actual depth of theobject being judged, and qualitative stereopsis, in which the depth is correctly nearer orfarther than the fixation point but the amount of depth does not grow with distance69 – Visual detection of motionMotion perception: is the process of inferring the speed and direction of elements in ascene based on visual, vestibular and proprioreceptive inputs. Although this processappears straightforward to most observers, it has proven to be difficult problem from acomputational perpective, and extradionarily difficult to explain in terms of neuralprocessing. Area V5 appers to be important to the processing of visual motion and damageto this area can disrupt motion perception. First order motion precerption: First order motion percerption refers to the perception of the motion of an objectthat differs in luminance from its background, such as black bug crawling across a whitepage. This sort of motion can be detected by relatively simple motion sensor designed todetect a change in luminance at one point on the retina and correlate it with change inluminance at a neighbouring point on the retina after a delay. Sensors that work thisway have been referred as Reichardt detectors, motion-energy sensors. These sensorsdetect motion by spatio-temporal correlation and are plausible models for how thevisual system may detect motion. First-order neurons sensors suffer from the apertureproblem, which means that they can detect motion only perpendicular to the orientation
73. of the contour that is moving. Further processing is required to disambiguate true globalmotion direction. Second-order motion precerption: Second –order motion is motion in which the moving contour is defined bycontrast, texture, flicker or some other quality that does not result in an increase inluminance or motion energy in the Fourier spectrum of the stimulus. There is muchevidence to suggest that early processing of first- and second- order motion is carriedout by separate pathways. Second-order mechanisms have poorer temporal resolutionand are low-pass in terms of the range of spatial frequencies that they respond to.Second order motion produces a weaker motion aftereffect unless tested withdynamically flickering stimuli. First and second order signals appear to be fullycombined at the level of area V5/MT of the visual system. Motion integration: Having extracted motion signals (first- and second- order) from the retinalimage, the visual system must integrate those individual local motion signals at variousparts of the visual field into a 2D or global represetation of moving objects and surfaces.Motion in depth: As in other aspects of vision, the observer´s visual input is generally insufficientto determine the true nature of stimulus sources, in this case their velocity in the realworld. In monocular vision for example, the visual input will be a 2D projection of a 3Dscene.70 – Functions of the tympanic membrane and middle ear ossicles. External Ear The external ear directs the sound vibrations in the air to the external auditorycanal. The sound waves travel through this auditory canal and vibrate the tympanicmembrane located at the end of the canal. Middle Ear Is a air-filled cavity in the temporal bone that opens via the auditory tube into thenasopharynx and throught the nasopharynx to the exterior. The middle ear acts toconserve the energy of the sound waves that strike the tympanic emmbrane, which istrasmitted to the cochlear fluid. It serves as a impedance matching device. It drasticallyreduces the surface area from the tympanic area to the stapes. 1. The tympanic membrane, is a thin membrane that separates the external ear from the middle ear. Its function is to transmit sound from the air to the ossicles inside the middle ear. The malleus bone bridges the gap between the eardrum and the other ossicles. In response to pressure changes produced by sound waves on its external surface, the tympanic membranes moves in and out. It functions as a resonator that produces the vibrations of the sound source. It almost stops vibrating almost immediately when the sound wave stops. The motions of the
74. tympanic membrane are imported to the manumbrium of the malleus and its short processes trasmitt the vibrations of the manubrium into the incus which moves in such a way that the vibrations are transmitted to the head of the staples. The movement of the head of the staples swing it footplate a door hanged at the post edge of the oval window and finally into the perilymph-filled scala vestibuli of the cochlea.. Rupture or perforation of the eardrum can lead to conductive hearing loss. 2. Three small bones (ossicles), which articulate with each other, are suspended in the cavity of the middle ear. These ossicles are the malleus (the cartilaginous process called manubrium of this bone is attached to the tympanic membrane), the incus, and the stapes. The stapes resembles a stirrup, and its footplate is bound to the oval window by an annular ligament. The middle ear is connected to the nasopharynx through the eustachian tube, which helps to equalize air pressure on the inner and outer surfaces of the tympanic membrane and to drain any fluid in the middle ear into the nasopharynx. A small muscle, the tensor tympani, inserts on the manubrium of the malleus; it is innervated by a branch of the trigeminal nerve (cranial nerve [CN] V). Another small muscle, the stapedius, inserts on the stapes ossicle and is innervated by a branch of the facial nerve (CN VII). Contraction of these muscles restricts the movement of the tympanic membrane and the footplate of the stapes against the oval window, respectively, and thus reduces the deleterious effects of loud noises on the delicate middle and inner ear structures. Therefore, the function of the middle ear and its components is to convert the sound waves in the air to waves in the fluid located in the inner ear. If the airwaves bypass the middle ear and reach the oval window directly, only about 3% of the sound would enter the inner ear. The pressure transmitted to the oval window is amplified because (1) the area of the tympanic membrane is much greater than that of the oval window, and (2) greater mechanical efficiency is provided by the ossicles (malleus and incus) because they act as levers.71 – Traveling wave in the cochlea. The cochlea is the auditory portion of the inner ear. Its core component is theOrgan of Corti, the sensory organ of hearing, which is distributed along the partitionseparating fluid chambers in the coiled tapered tube of the cochlea. Air pressure waves cause the tympanic membrane to vibrate, resulting inoscillatory movements of the footplate of stapes against the oval window. Because theperilymph is a noncompressible fluid and the scalae tympani and vestibuli form a closedsystem, oscillatory movements of the stapes against the oval window result in pressurewaves in the perilymph present in the scalae tympani and vestibuli. The oscillatorymovement of perilymph results in vibration of the basilar membrane. As mentioned earlier, the tips of the stereocilia (of the outer hair cells) areembedded in the tectorial membrane, and the bodies of hair cells rest on the basilarmembrane. An upward displacement of the basilar membrane creates a shearing forcethat results in lateral displacement of the stereocilia. Mechanical displacement of the +stereocilia and kinocilium in a lateral direction causes an influx of K through their 2+membranes, the hair cell is depolarized, and there is an influx of Ca through the
75. 2+ 2+voltage-sensitive Ca channels in their membranes. The influx of Ca triggers therelease of the transmitter (probably glutamate) that, in turn, elicits an action potential inthe afferent nerve terminal at the base of the hair cell. A downward displacement of thebasilar membrane creates a shearing force that results in medial displacement of thestereocilia and kinocilium. Mechanical displacement of the stereocilia and kinocilium ina medial direction results in hyperpolarization of the hair cell that may involve opening + +of voltage-sensitive K channels and efflux (outward flow) of K . The sensory receptors(hair cells) located in the basal portion of the basilar membrane respond to highfrequencies of sound, while the sensory receptors located in the apical aspect of themembrane respond to low frequencies. This is called tonotopic distribution ofresponding receptors. 1. A high frequency wave travels only a short distance and then dies out. 2. A medium frequency wave travels half ay and dies out 3. A low frequency wave travels the entire distance.72 – Functions of the inner ear and outer cochlear hair cells. The hair cells ia an evolutionary triumph that solves the problem of trasformingvibrational energy into eletrical signal. The inner ear contains the cochlea that converts sound waves into neural signals-these signals are passed to the brain via the auditory nerve. There are two types of hair cells: inner hair cells and outer hair cells. The bottomof these cells are attached to the basilar membrane and the stereocilia are in contact withthe tectorial membrane. Inside the cochlea, sound waves causes the basilar membrane tovibrate up and down and this creates a shearing force between the basilar membrane andthe tectorial membrane causing the hair cell stereocilia to move. This leads to internalchanges within the hair cells that creates eletrical signals. The stereocilia of the outer hair cells are inserted into the gelatinous tectorialmembrane, so that vibration of the basilar membrane causes oscillations of the hairs andtherefore oscillation of the membrane potential of hair cells.
76. The inner hair cells are the primary sensory cells that generate action potentialsin the auditory nerves, and presumably they are stimulated by the fluid movementsnoted above. The outer hair cells respond to sound, like the inner hair cells, but depolarizationmakes them shorten and hyperrepolarization makes them leghten. They do this over thevery flexible part of the basal membrane and this action somehow increases theamplitude and clarity of sounds. The outer hair cells receive cholinergic innervation (acetylcholine) via anefferent component of the auditory nerve and that hyperrepolarizes the cells. There are two types of supporting epithelial cells that keep the hair cells inposition: the phalangeal cells and pillar cells. The outer phalangeal cells (Deiters cells)surround the base of the outer hair cells and the nerve terminals associated with thesecells. These cells give out a phalangeal process. This process flattens into a plate nearthe apical surface of the hair cell and forms tight junctions with the apical edges ofadjacent hair cells and adjacent phalangeal plates. The inner phalangeal cells surroundthe inner hair cell completely and do not have a phalangeal process. Similarly, there areouter and inner pillar cells whose apical processes form tight junctions with each otherand with neighboring hair cells. This network of tight junctions isolates the body of thehair cells from the endolymph contained in the scala media. The spiral (cochlear)ganglion, located within the spiral canal of the bony modiolus, contains bipolar neurons.The peripheral processes of these bipolar neurons in the spiral ganglion innervate thehair cells; they form the postsynaptic afferent terminals at the base of the hair cell. Thecentral processes of the bipolar cells in the spiral ganglion form the cochlear division ofCN VIII. The outer hair cells receive efferent fibers that arise from the superior olivarynucleus (called the olivocochlear bundle). This bundle provides a basis by which thecentral nervous system can modulate auditory impulses directly at the level of thereceptor.73 – Transduction of an auditory signal. Air pressure waves cause the tympanic membrane to vibrate, resulting inoscillatory movements of the footplate of stapes against the oval window. Because theperilymph is a noncompressible fluid and the scalae tympani and vestibuli form a closedsystem, oscillatory movements of the stapes against the oval window result in pressurewaves in the perilymph present in the scalae tympani and vestibuli. The oscillatorymovement of perilymph results in vibration of the basilar membrane. The tips of the stereocilia (of the outer hair cells) are embedded in the tectorialmembrane, and the bodies of hair cells rest on the basilar membrane. An upwarddisplacement of the basilar membrane creates a shearing force that results in lateraldisplacement of the stereocilia. Mechanical displacement of the stereocilia and +kinocilium in a lateral direction causes an influx of K through their membranes, the 2+ 2+hair cell is depolarized, and there is an influx of Ca through the voltage-sensitive Ca
77. 2+channels in their membranes. The influx of Ca triggers the release of the transmitter(probably glutamate) that, in turn, elicits an action potential in the afferent nerveterminal at the base of the hair cell. A downward displacement of the basilar membranecreates a shearing force that results in medial displacement of the stereocilia andkinocilium. Mechanical displacement of the stereocilia and kinocilium in a medialdirection results in hyperpolarization of the hair cell that may involve opening of + +voltage-sensitive K channels and efflux (outward flow) of K . The sensory receptors(hair cells) located in the basal portion of the basilar membrane respond to highfrequencies of sound, while the sensory receptors located in the apical aspect of themembrane respond to low frequencies-tonotopic distribution of responding receptors. The inner hair cells trasmitt the information to the acoustic nerve.74 – Draw and describe simplified scheme of a neuronal chain of pathways forhearing.The auditory nerve carries the signal into the brainstem and synapses in the cochlear nu-cleus. Auditory nerve fibers going to the ventral cochlear nucleus (uniform neuronswith carry information about intensity of sound and direction of sound) synapse on theirtarget cells. The ventral cochlear nuclear cells then project to a collection of nuclei inthe medulla – superior olive. Superior olive: − Ipsilateral input: excitation
78. − Contralateral input: inhibition through interneurons od ncl. corporis trapezoide. The minute differences in the timing and loudness of the sound in each ear arecompared and from this one can determine the direction the sound comes from. The superior olive lies in the caudal pons, near the facial motor nucleus. It is thenucleus in the brainstem where auditory inputs from the ears converge. This conver-gence is essential for localization of sound, and for the construction of neural maps ofcontralateral auditory hemifields. The superior olive projects up to the inferior colliculus via a fiber tract called lat-eral lemniscus. Dorsally situated cochlear nuclei cells project to the contralateral inferior col-liculus while simpler ventral cells project to the superior olive and appears to processlocalization of sounds.Nucleus cochlearis dorsalis: Heterogeneous neurons, dispose tonotropic arrangment and direct connect to nu-cleus colliculi inferior. It differentiates the pich of tone. This pathway projects directlyto the inferior colliculus also via lateral lemmniscus.Nucleus colliculi inferiores. Important in integration of space information from the nucleus olivaris superi-ores and integration of sound intensity and pitch of tone. Nucleus corporis geniculate medial: Tonotropic arrangment Descendant auditory pathway From auditory cortex and nucleus leads to rise of sensitivity or suppression ofextreme inputs. The auditory cortex send efferent fibers to the ipsilateral medial genicu-late nucleus and to the external nucleus of inferior colliculus that sends efferents fromits central nucleus to the ipsilateral and contralateral olivary nucleus and to dorsalcochlear nucleus. Fibers travel from the olivary nuclei in the olivocochlear bundle, in the vestibu-lar part of the vestubulocochlear nerve. − Lateral olivocochlear fibers terminate at ipsilateral inner hair cells. − Medial olivocochlear fibers terminate at ipsilateral and contralateral out- er hair cells.
79. Descending pathways appear to be important in the filtering of auditory informa-tion at all levels of the CNS, and even down to the cochlea. This filtering is importantin, for example in the discrimination between background noises and these that listenerwishes to concentrate on.75 – Localization of sound in space.The circuits that compute the position of a sound source on this basis are found in the: . Lateral superior olive (LSO). . Medial nucleus of the trapezoid body (MNTB) Excitatory axons project directly from the ipsilateral anteroventral cochlear nuc-leus to the lateral superior olive. Note that the lateral superior olive also receives inhibit-ory input from the contralateral ear, via an inhibitory neuron in the medial nucleus ofthe trapezoid body. This excitatory/inhibitory interaction results in a net excitation ofthe lateral superior olive on the same side of the body as the sound source. For sounds
80. arising directly lateral to the listener, firing rates will be highest in the lateral superiorolive on that side, in this circumstance, the excitation via the ipsilateral anteroventralcochlear nucleus will be maximal, and the inhibition from the contralateral medial nuc-leus of the trapezoid body will be minimal.1. Stronger stimulus to left ear excites left lateral superior olive. This stimulus also in-hibits right lateral superior olive via medial nucleus of the trapezoid body interneuron.2. Excitation from the left side is greater than inhibition from right side, resulting a netexcitation to higher centres.76 – Sense of balance – stimuli, receptors cells. Our sense of balance is regulated by a complex interaction of the following partsof the nervous system: 1. The inner ears (also called the labyrinth) monitor the directions of motion, such as turning or forward-backward, side-to-side, and up-and- down motions. 2. The eyes observe where the body is in space (i.e., upside down, right side up, etc.) and also the directions of motion.
81. 3. Skin pressure receptors such as those located in the feet and seat sense what part of the body is down and touching the ground. 4. Muscle and joint sensory receptors report what parts of the body are moving. 5. The central nervous system (the brain and spinal cord) processes all the bits of information from the four other systems to make some coordinated sense out of it all. Vestibular labyrinth The vestibular system has two major components, one made by threesemicircular canals filled with endolimph, a special type of extracellular fluid, thatmeasure angular velocity of the head (the speed with which we turn our head on itsaxis), and another component is made up by the saccule and utricle, which are two saclike bulges, and are responsible for detecting linear velocity. The three semicircularcanals are all perpendicular to each others plane, forming a three dimensionalrepresentation of all possible head movements. The ability to detect angular velocityderives from the fact that when we rotate our heads in any direction, the liquid insidethe corresponding canal to the plane of movement tends to stay put, due to inertia. Atthe base of each semicircular canal lies a dilatation of the canal called ampulla, andinside the ampulla there is a thickening of the epithelium that contains the specializedreceptor cells, called vestibular hair cells. On this thickening there is a diaphragm-likegelatinous mass that covers the lumen of the canal, called the ampullary crest. The crestis deformed by the endolimph when some angular force is exerted, and itself deformsthe cilia (hair like protuberances) of the vestibular hair cells. The cilia of these cells arenot symmetrically arranged on the surface and have a conformation such that allows78 – Responses to angular and linear acceleration. When the head suddenly begins to rotate in any direction (angular accelera-tion), the endolymph in the semicircular ducts, because of its inertia, tends to remainstationary while the semicircular ducts turn. This causes relative fluid flow in the ductsin the direction opposite to head rotation. There is a typical discharge signal from a single hair cell in the crista ampullariswhen an animal is rotated for 40 seconds, demonstrating that:
82. 1. even when the cupula is in its resting position, the hair cells emits a tonic dis- charge of about 100 impulses per second. 2. When the animal begins to rotate, the hairs bend to one side and the rate of dis- charge increases greatly 3. with continued rotation, the excess discharge to the hair cell gradually subsides back to the resting level during the next few seconds. The reason for this adaptation of the receptor is that within the first few secondsof rotation, back resistance to the flow of fluid in the semicircular duct and past the bentcupula causes the endolymph to begin rotating as rapidly as the semicircular canal itself.Then, in another 5 to 20 seconds, the cupula slowly returns to its resting position in themiddle of the ampulla because of its own elastic recoil.When the rotation suddenlystops, exactly opposite effect takes place: the endolymph continues to rotate while thesemicircular duct stops. This time, the cupulla bends in the opposite direction, causingthe hair cell to stop discharging entirely. After another few seconds the endolymphstops moving and the cupulla gradually returns to its resting position, thus allowing haircell discharge to return to its normal tonic level. Thus, the semicircular duct transmits asignal of one polarity when the head begins to rotate and of opposite polarity when itstops rotating.Detection of linear acceleration by the ultricle and saccule maculae:When the bodyis suddenly thrust forward – that is, when the body accelerates – the statoconia, whichhave greater mass ineria than the surronding fluid, fall backward on the hair cell cilia,and information of dysequilibrium is sent into the nervous centers, causing the person tofeel as though he or she falling backward. This automatically causes the person to leanforward until the resulting anterior shift of the statoconia exactly equals the tendency forthe statoconia to fall backward because of the acceleration.79 – Describe hierarchic organization of motor systems, classes of movements. Classification of motor controls: 1. Voluntary movement: complex, targeted and purposeful movements. - stimulation by our decision (volition) - reaction to determinated specific and external stimuli. - Hone by learning.
83. 2. Reflex movement: simple movement reations to external stimuli - a minimal influence by our decision (volition). - a stereotypical movement and fast (supporting movement) 3. Rhytmic motor patterns: beginning and finishing by own decision (volition). - proper movement is stereotypical, robotic based on given reflex Other classification of motor control: 1. Supporting movement: maintain posture and position of body 1. Target motor movement: serve to obtain food. - is related to human work. - Serve to communicate in motor control of speech. 2. Emotional motor control: motor expression of own emotions - serve to communication. Hierarchical organization:Motor cortex Cerebellum and basal ganglia brain stem spinal cord Skeletal muscles80 – Sensory information necessary for the control of movements Structural supplying control of movements: -Spinal cord -Brainstem (NR, SN, FR, olivary nucleus, vestibular nucleus) -Cortex -Cerebellum
84. -Basal ganglia - Motor thalamus (nucleus ventralis anterior et lateralis) Lower motorneurons – Brainstem - Somatomotor zone: ncl. Originis n. III, IV, VI, XII - Brachiomotor zone: ncl. Originis n. V, VII, IX, X motor unit: a connection of one motorneuron (spinal cord or brainstem) by its axon with a number of muscle fibers. - small motor unit: one motorneuron innervates a few muscle fibres (oculomotor,distal muscle of upper extremity ) - large motor unit: one motorneuron innervates about 500-1000 muscle fibers, e.g.back muscles. Motor systems for control movement:- Medial system: brainstem pathways and cortical pathways.- Lateral system: brainstem pathways and cortical pathways.- The 3rd motor systemNeural centers responsible for movement: The neural circuits responsible for the control of movement can be dividedinto four distinct substystems: 1, 2 upper 3 qnd 481 – Muscle spindles and Golgi tendon organs, structure and function. Muscle Spindles Muscle spindles are present in skeletal (flexor as well as extensor) muscles.They are more numerous in muscles that control fine movements (e.g., muscles of thehands and speech organs and extraocular muscles). Each spindle consists of aconnective tissue capsule in which there are 8 to 10 specialized muscle fibers calledintrafusal fibers. The intrafusal fibers and the connective tissue capsule in which theyare located are oriented parallel to the surrounding skeletal muscle fibers calledextrafusal fibers. The intrafusal fibers are innervated by spinal gamma motor neurons,
85. whereas the extrafusal fibers receive motor innervation from alpha motor neuronslocated in the spinal cord. There are two types of intrafusal fibers. The nuclear chainfiber contains a single row of central nuclei and is smaller and shorter than the nuclearbag fiber. The nuclear bag fiber has a bag-like dilation at the center where a cluster ofnuclei is located. Efferent innervation is provided to the polar ends of both types ofintrafusal fibers (i.e., nuclear bag and nuclear chain fibers) by efferent axons of gammamotor neurons that are located in the ventral horn of the spinal cord. Two types of afferents arise from the intrafusal fibers: 1. annulospiral endings (primary afferents), which are located on the central part of the nuclear bag and nuclear chain fibers; and 2. flower-spray endings (secondary afferents), which are located on both types of intrafusal fibers on each end of the annulospiral endings. Annulospiral endings are activated by brief stretch or vibration of the muscle, whereas both types of afferent endings (annulospiral and flower-spray) are activated when there is a sustained stretch of the muscle. Thus, muscle spindles detect changes in the length of the muscle.) Golgi Tendon Organ These high-threshold receptors are located at the junction of the muscle and ten-don. Golgi tendon organs are arranged in series with the muscle fibers, in contrast tomuscle spindles, which are arranged parallel to the extrafusal muscle fibers. A tendon iscomposed of fascicles of collagenous tissue that are enclosed in a connective tissue cap-sule. A Golgi tendon organ consists of a large myelinated fiber that enters the connec-tive tissue capsule of a tendon and subdivides into many unmyelinated receptor endingsthat intermingle and encircle the collagenous fascicles. Active contraction of the muscleor stretching of the muscle activates the Golgi tendon organs. Thus, Golgi tendon or-gans are sensitive to increases in muscle tension caused by muscle contraction. Unlikemuscle spindles, they do not respond to passive stretch. Activation of the Golgi tendonorgan produces a volley in the associated afferent fiber (called a Ib fiber). This afferentfiber makes an excitatory synapse with an interneuron that then inhibits the alpha motorneuron, which innervates the homonymous muscle group. The net effect is that the peri-od of contraction of the muscle in response to a stretch is reduced. This type of response(i.e., reduction of contraction of homonymous muscle) elicited by stimulation of Golgitendon organs is referred to as the inverse myotatic reflex.82 – Alpha and gamma motoneurons, their function The voluntary (striated, skeletal) muscles are innervated by alpha motoneurons,which have heavily myelinated, fast-conducting axons that terminate in motor endplates of extrafusal striated muscle fibers. Because these neurons are the only pathwaythrough which the sensory systems and the descending upper motoneuron pathways ofthe CNS exert their influences upon striated muscles, they function as the final commonpathway, the final link between the CNS and the voluntary muscles. The intrafusal
86. striated muscles of the muscle spindles are innervated by gamma motoneurons, whichhave lightly myelinated, slow-conducting axons. The term lower motoneuron, as used inclinical neurology, refers to motor neurons that innervate the voluntary muscles.Destruction of the lower motoneurons results in abolishing voluntary and reflexresponses, rapid atrophy, and flaccid paralysis of the muscles innervated; these signs arereferred to as a lower motoneuron paralysis. The lower motoneurons have their cellbodies within the anterior horn of the spinal cord and in the motor nuclei of thebrainstem; the latter innervate voluntary muscles supplied by the cranial nerves (e.g.,muscles of facial expression). The term upper motoneuron refers to descending motorpathways within the CNS that either directly or indirectly exerts influences onlower motoneurons. The activities of alpha and gamma motoneurons are affected byinputs from peripheral receptors via the spinal and cranial nerves and from uppermotoneurons. At spinal cord levels, local interneurons, part of intrasegmental andintersegmental circuits within the gray matter, exert both excitatory and inhibitoryinfluences on these lower motoneurons. Several differences exist between alpha and gamma motoneurons:1. Alpha motoneurons can be stimulated monosynaptically (i.e., directly, not throughinterneurons) by groups Ia and II afferent fibers from muscle spindles and by someterminals of the corticospinal, lateral vestibulospinal and medullary reticulospinaltracts. Gamma motoneurons are not stimulated monosynaptically.2. Alpha motoneurons emit axon collaterals that terminate on Renshaw cells, which inturn, have inhibitory synapses with the same alpha motoneurons. This forms a negativefeedback circuit that serves to turn off an active alpha motoneuron so that it83 – Describe a neuronal chain of the medial pathways from the brainstem that in-fluence the spinal motorneurons, cite their functions. Function of medial motor pathways of brainstem. Postural motor control, coordination of head and eye movements. - Tractus tectospinalis: projection to neck spinal segments.
87. - Tractus cortico-tecto-spinalis: coordination of head and eye movements during object observation. - Tractus reticulospinalis medialis: from pontinal reticular formation-activation of extensors (their tonus)-primary activation of gamma loop. - Tractus reticulospinalis lateralis: activation and inhibition of extensors - Tractus cortico-reticulo-spinalis: for cortical control of spinal reflexes. - Tractus vestibulospinalis: terminate to gamma ʎ and alpha α motorneurons, dir- ect conytol of α motorneurons (clinical importance in α rigidity) - Nucleus vestibularis lateralis (Deiters) / tractus vestibulospinalis lateralis: de- creases ipsilaterally to lower motorneurons. Facilitation of extensors with reciprocal inhibition. - Nucleus vestibularis medialis (Schwalbe) / tractus vestibularis medialis: de- creases bilaterally to cervical and thoracic lower motorneurons. Control of neck and body muscles. - from cerebellar cortex: inhibition of ncl.vestibularis. A non-functional cerebellum leads to uncontrolled excitation of α motornreurons84 – Describe a neuronal chain of the lateral pathways from the brainstem that in-fluence the spinal motorneurons, cite their functions.- Tractus rubropinalis: main route for mediation of voluntary movement. It’s respons-ible for large muscle movement. Also facilitates flexion and inhibits extension in theupper extremity
88. - Red nucleus serves as an alternative pathway for transmitting cortical signals to thespinal cord. It is located in the mesencephalon, function in close association with thecorticospinal tract.- The red nucleus receives a large number of direct fibers from the primary motor cortexthrough the corticorubral tract, as well as branching fibers from the corticospinal tract.These fibers synapse in the lower portion of the red nucleus, the magnocellular portion,which contain large neurons. These neurons give rise to the rubrospinal tract whichcrosses the opposite side in the lower brain stem and follows a course immediately adja-cent and anterior to the corticospinal tract into the lateral columns of the spinal cord.- The red nucleus projections are limited to the cervical level of the cord, but these ter-minate in lateral regions of the ventral horn and intermediate zone. The axons arisingfrom the red nucleus participate together with lateral corticospinal axons in the controlof the arms. The limited distribution of rubrospinal projections may seem surprisingly,given a large size of the red nucleus in humans.85 – Describe a neuronal chain of the medial cortical pathways that influence thespinal motorneurons, cite their function. Tractus corticospinalis anterior (a 6 a 4) Axons run bilaterally to medial group of lower motornurons. Involved in voluntaryinnervation of neck, body and proximal muscles of the extremity. Send collaterals toneurons of medial motor system of brainstem (tractus cortico-vestibulo-spinalis, tractiscortico-reticulo-spinalis). Motor cortex I
89. A) Primary motor cortex (MC) - a4 gyrus precentralis - somatrotopic arrangement - direct excitatory influence of motor neurons of distinct motor units - through interneurons-inhibitory influence of motorneurons - neuron activation before realized movement-power of contraction - output from cortical motorneurons is controlled according to desiderative power of contraction. B) Premotor cortex (PMC) – a 6 Lateral surface of frontal lobe - control of medial brainstem system - control of proximal muscles of extremities, orientation of trunk and extremities before execution of movementC) Supllementary motor are (SRA) – a 6 (at the medial surface of the frontal lobe) - stimulation: complex movements - plan of coordinated movements by distal muscles - appreciation of movement Corticospinal tract: originates about 35% of axons from neurons of area 4(gyrus precentalis – Primary motor cortex) and 30% of axons from neurons of area 6(Lateral surface of the fronyal lobe – Premotor cortex and supllementay motor areas.) - A few fibers do not cross to the opposite side un the medulla but pass ipsilaterallydown the cord in ventral (medial) vorticospinal tract-these fibers may be concerned withcontrol of bilateral postural movements by the supplementart motor cortex.86 – Descrive a neuronal chain of the lateral cortical pathways that nfluence thespinal motorneurons, cite their function. Tractus corticospinalis lateralis (a 4) • direct control of activity of contralateral lower motorneurons innervating distal muscles of extremities (voluntary movements).
90. • send collaterals to nucleus runner – tractus corticico-rubro spinalis • after leaving the cortex, it passes through the posterior limb of the intern- al capsule (between the caudate nucleus and the putamen of the basal ganglia) and then downward through the brain stem, turning the pyram- ids of the medulla. • the majority of the pitamidal fibers then cross in the lower medulla to the opposite site and descend into the lateral corticospinal tracts of the cord, finally terminating principally on the interneurons in te intermediate re- gions of the cord gray matter. A few terminate on sensory relay neurons in the dorsal horn.87 – Describe afferent, efferent and internal connectins of the basal ganglia. The primary function of the basal ganglia is to provide a feedback mechanism tothe cerebral cortex for the initiation and control of motor responses. Much of the outputof the basal ganglia, which is mediated through the thalamus, is to reduce or dampen theexcitatory input to the cerebral cortex. When there is a disruption of this mechanism,disturbances in motor function ensue. The basic core circuit comprises: cerebral cortex → striatum → globus pallidus→ thalamus → cerebral cortex. Processed information then is transmitted via uppermotoneuron pathways (e.g., corticospinal tract) to the lower motoneurons. Afferent Sources of the Basal Ganglia
91. The largest afferent source of the basal ganglia arises from the cerebral cortex. In fact,most regions of the cortex contribute projections to the basal ganglia. These includeinputs from motor, sensory, association, and even limbic areas of the cortex. While thecaudate nucleus and putamen serve as the primary target regions of afferent projectionsfrom the cortex, the source of cortical inputs to these regions of the basal ganglia differ.The principal inputs from the primary motor, secondary motor, and primarysomatosensory regions of cortex are directed to the putamen.Internal Connections of the Basal Ganglia The most salient of the connections include the following: (1) the projections from the neostriatum to the globus pallidus; (2) the reciprocal relationships between the neostriatum and substantia nigra; (3) the reciprocal relationships between the globus pallidus and the subthalamicnucleus. Connections of the Neostriatum with the Globus Pallidus There are two basic projection targets of the neostriatum: the globus pallidus andthe substantia nigra. The neostriatum projects to two different regions of the globuspallidus: the medial (internal) pallidal segment and the lateral (external) pallidalsegment. GABA mediates the pathway from the neostriatum to the medial pallidalsegment; Connections of the Neostriatum with the Substantia Nigra The substantia nigra has two principal components: a region of tightlycompacted cells, called the pars compacta, and a region just ventral and extendinglateral to the pars compacta, called the pars reticulata. Fibers arising from theneostriatum project to the pars reticulata. Transmitters identified in this pathway are. Connections Between the Globus Pallidus and Subthalamic Nucleus Globus pallidus shares reciprocal connections with the subthalamic nucleus. Thelateral segment of the globus pallidus (which receives GABAergic and enkephalinergicinputs from the neostriatum) projects to the subthalamic nucleus. GABA also mediatesthis pathway. In turn, the subthalamic nucleus projects back to the medial segment ofglobus pallidus. This pathway, however, is mediated by glutamate.Output of the Basal Ganglia The basal ganglia influence motor functions primarily by acting on motorneurons of the cerebral cortex via relay nuclei of the thalamus. The output pathways ofthe basal ganglia achieve this.88 – Describe four gunctional loops of the basal ganglia. Functional loops of basal ganglia: 1) Sensory motor-loop 2) Association (pre-frontal) loop 3) Limbic loop 4) Oculomotor loop
92. • Sensory-motor loop: Widespread areas of the cerebral cortex, including the motor areas, projectcorticostriate fibers in a topographically organized arrangement to the ipsilateralstriatum, particularly the putamen.Association (prefrontal) loopThe association circuit is different from the motor and oculomotor circuits in that thewidespread association areas of the frontal, parietal, occipital, and temporal lobesproject primarily to the ipsilateral caudate nucleus. The closed loop commences andends in the prefrontal region (areas 9 and 10). Further, striatopallidal connections to themedial segment of the globus pallidus terminate in portions of the nucleus that projectpreferentially to intralaminar nuclei other than the CM, as well as to the VA and VL. Inaddition to diffuse cortical collaterals, these other intralaminar nuclei project back to thecaudate. Also, the parts of the VA and VL receiving input forward the information tothe prefrontal cortex (areas 9 and 10). • Oculomotor loop The closed-loop component of the oculomotor circuit begins and ends in thefrontal eye field (area 8). The open loop receives input from the prefrontal cortex (areas9 and 10) and from the posterior parietal region (area 7). Fibers arising from thesecortical areas project preferentially to the body of the caudate nucleus, from which, afterprocessing, information is sent to the globus pallidus and the substantia nigra, the parsreticularis. In addition to projections from these nuclei to the thalamus as in the othercircuits (VL, VA, intralaminar), nigral efferents also go to the frontal eye field (area 8)via relays in the dorsomedial nukleus of the thalamus and directly to the superiorcolliculus to participate in control of saccadic eye movement • Limbic loop There are several separate circuits that can be described as limbic, but they havebeen combined into one for simplification. The closed-loop portion of a limbic circuitbegins and ends in the anterior part of the cingulate gyrus (area 24) and orbitofrontalcortex (areas10 and 11). 89 – Describe structural-functional compartments of the cerebellum (hori-zontal and longitudinal divisions) The cerebellum consists of : (1) an outer gray mantle, the cortex, (2) a medullary core of white matter composed of nerve fibers projecting to andfrom the cerebellum, and
93. (3) four pair of deep cerebellar nuclei (fastigial, globose, emboliform, anddentate). The globuse and emboliform nuclei together constitute the interposed nucleus The cerebellar cortex consists of two large bilateral hemispheres connected by anarrow median portion called the vermis. This transverse organization is furthersubdivided into three zones: medial or vermal; paramedial, paravermal, or intermediate;and lateral or hemispheric. In addition to the cortex, each zone consists of underlyingwhite matter and a deep cerebellar nucleus to which it topographically projects vermisto fastigial nucleus, paravermal cortex to interposed nuclei, and hemisphere to dentatenucleus Functionally, the cerebellum can usefully be considered as three separate compart-ments-each consisting of an area of cerebellar cortex together these are the: - Vestibulocerebellum (consists of the floculonodular node and adjacent areas ofthe vermis). - spinocerebellum. - pontocerebellum. - Vestibulocerebellum: (in horizontal division) - receives afferents from the vestibular nucleus and the ipsilateral vestibular gangli-on - vestibulocerebellar outflow is concerned chiefly with the orientation of the headand body in space, and with certain eye movements - Spinocerebellar nodule (in longitudinal division) - consists of the intermediate and adjacent vermian zone. - receives its input from ascending spinocerebellar and cuneocerebellar tract. - fibers that enter the vermian zone project collaterals to fastigial nucleus. - Pontocerebellar nodule (in horizontal fivision) - is the largest zone and consists of the lateral area. - receives most of its inputs as crossed afferents from the basal pontine nucleithrough the middle cerebellar peduncle.90 – Describe connections of the vestibular cerebellum and its involvement in themotor control. Both the vestibular system and reticular formation play important roles in theregulation of motor processes that primarily affect extensor muscles and that relate to
94. the control of balance and posture. Both of these regions also contribute significant in-puts to the cerebellum. Vestibular System The cerebellum receives signals from the otolith organ (i.e., macula of sacculeand utricle) and semicircular canals of the vestibular system. Fibers arising from thevestibular apparatus may enter the cerebellar cortex via a monosynaptic or disynapticpathway. The monosynaptic pathway (called the juxtarestiform body) involves first-or-der vestibular neurons that terminate within the ipsilateral flocculonodular lobe. Thesecond route involves primary vestibular fibers that synapse in the vestibular nuclei andsecond-order neurons that project chiefly from the inferior and medial vestibular nucleito the same region of cerebellar cortex. In this manner, the cerebellum receives import-ant information concerning the position of the head in space at any given point in timeas well as the status of those vestibular neurons that regulate extensor motor neurons(via the vestibulospinal and reticulospinal tracts). There is a further differentiation offunction within the cerebellar cortex in that the flocculonodular lobe represents the spe-cific receiving area for vestibular inputs, and the anterior lobe is the primary receivingarea for spinal cord afferents. The projections to the vestibular nuclei (the only projections from the cerebellarcortex to a noncerebellar site) indicate that these nuclei are similar to deep cerebellarnuclei. The medial vestibular nucleus gives rise to the medial vestibulospinal tract of themedial descending system. A few fibers from the fastigial nucleus ascend and passthrough the superior cerebellar peduncle and terminate in the contralateral VL nucleus.These VL neurons project to those sites of primary motor cortex that give rise to theanterior corticospinal tract of the medial descending system91 – Describe connections of the spinal cerebellum (median zone) and its involve-ment in motor control. Circuitry Associated With the Vermis (Vermal Zone)
95. Somatic sensory information from the body and limbs is conveyedsomatotopically via the dorsal spinocerebellar and cuneocerebellar tracts to the cortex ofthe vermis. In addition, afferent input from the head is derived from the spinaltrigeminal nucleus and vestibular, auditory, and visual systems. The vermal cortexprojects to the fastigial nucleus, which, in turn, projects to two different regions viafibers passing through the inferior cerebellar peduncle. (1) The largest number of fibersterminate in the vestibular nuclei and a substantial group descends in the juxtarestiformbody and central tegmental tract of the brainstem to pontine and medullary reticularnuclei. (2) A few fibers ascend and terminate mainly in the contralateral ventral lateral(VL) nucleus of the thalamus. Projections from this part of the VL ascend and terminatein the regions of the primary motor cortex, which give rise to the anterior corticospinaltract. The pontine and medullary reticular nuclei give rise respectively to the medial andlateral reticulospinal tracts. All three of these tracts belong to the medial descendingsystems, which terminate in the medial column of spinal gray matter where lowermotoneurons innervating axial musculature are located. Note the linkage between thevermis (vermal zone) and the control of the axial and girdle musculature. Purkinje cellsin the vermis also project to the ipsilateral lateral and inferior vestibular nuclei92 – Describe connections of the spinal cerebellum (paramedian zone) and its in-volvment in the motor control.Circuitry Associated With Intermediate Hemisphere (Paravermal Zone)
96. The dorsal spinocerebellar tract, which conveys signals mainly from musclespindles and Golgi tendon organs concerning the status of individual muscles to thecerebellar cortex from the lower limbs, passes through the inferior cerebellar peduncleand terminates mainly in the medial part of the ipsilateral anterior lobe and adjacentportions of the posterior lobe Somatic sensory information is conveyed via the dorsal spinocerebellar andcuneocerebellar tracts to the cortex of the intermediate lobe. This cortex projects to theinterposed nuclei, which give rise to fibers that pass through the superior cerebellar ped-uncle and cross in the decussation of the superior cerebellar peduncle. Some fibers ter-minate in the magnocellular portion of the red nucleus.Others ascend and terminate inthe VL. The ventrolateral nucleus projects to the primary motor cortex (area 4) and thesupplementary motor cortex (area 6). The lateral descending system originates fromthese sources, the rubrospinal tract originates from the magnocellular portion of the nuc-leus ruber, and the lateral corticospinal tract originates from the primary motor and sup-plementary cortices. These tracts control the activity of the musculature of the extremit-ies. There is a important connection between the intermediate hemisphere and control ofmusculature of the extremities. 93 – Describe the connections of the pontocerebellum and its involvement inthe motor control. The primary route by which the cerebral cortex communicates with the cerebel-lar cortex is via a relay in the basilar (ventral) pons. Fibers arising from all regions ofthe cerebral cortex project through the internal capsule and crus cerebri, making syn-aptic connections upon deep pontine nuclei. The deep pontine nuclei give rise to axons
97. called transverse pontine fibers that enter the contralateral middle cerebellar peduncleand are distributed to the anterior and posterior lobes of the cerebellum. The largest component of the projection to the cerebellar cortex arises from thefrontal lobe. This provides the primary substrate by which motor regions of the cerebralcortex can communicate with the cerebellar cortex. However, sensory regions of thecerebral cortex also contribute fibers to the cerebellar cortex. These include parietal,temporal, and visual cortices. The posterior parietal cortex provides the cerebellum withinformation concerning the planning or programming signals that are transmitted to themotor regions of the cerebral cortex. Temporal and occipital cortices provide the cere-bellar cortex with signals associated with auditory and visual functions. In particular,the connection from the visual cortex may signal such events as moving objects in thevisual field. Visual and auditory signals may also reach the cerebellar cortex from thetectum. Somatosensory signals also reach the cerebellar cortex from the cerebral cortex.Evidence suggests that fibers from the sensorimotor cortex are somatotopically arrangedwithin the vermal and paravermal regions of the cerebellar cortex in a manner that cor-responds to the somatotopic organization associated with spinal cord inputs.94 – Describe pathways for the vestibulo-optic reflexes. • Vestibulo-ocular-reflex (VOR) - is a mechanism for producing eye movements that canter head movements thus permitting the gaze to remain fixed on a particular point. (e.g. activity in the left
98. horizontal canal induced by leftward rotatory acceleration of the head that ex- cites neurons in the left vestibular nucleus that results in compensatory mechan- ism eye movements to the right. - this effect is due to excitatory projections from the vestibular nucleus to the contralateral nucleus abducens that, along with the oculomotor nucleus, help ex- ecute conjugate eye movements. - for instances, horizontal movement of the two eyes toward the right requires contraction of the left medial and right lateral rectus muscles. - Vestibular nerve fibres-originating in the left horizontal semicircular canal, project to vestibular nuclei (medial and lateral) - excitatory fibers from the medial vestibular nucleus cross to the contralateral abducens nucleus which has two outputs: 1) motor pathway that causes the lateral rectus of the right eye to contract 2) an excitatory projection that crosses the midline and ascends via the medial longitudinal gfasciculus to the left occulomotor nucleus where it activ- ates neurons to cause the medial rectus of the left eye to contract. -inhibitory neurons project from the medial vestibular nuclei to the left abducens nucleus, directly causing the motor drive on the lateral rectus of the eye to de- crease and also indirectly causing the right medial rectus to relay. The con- sequence of these several connections is that excitatory input from the horizontal canal on one side produces eye movements toward the opposite side. Therefore, turning the head to the left causes eye movements to the right. • Neural control of smooth pursuit movements Smooth pursuit movements are also mediated by neurons in the pontine reticularformation but are under the influence of motor control cortex other than the superiorcolliculus and frontal eye field. The superior colliculus and frontal eye field are exclus-ively involved in generation of saccades95 – Describe pathways for a control of slow eye movement- The eyes may move indentically (conjugate movements – simultaneous movement ofboth eyes in the same direction).- But the eyes can move in opposite directions (disconjugate movements) when conver-ging or diverging to focus on moving objects and keep them focused on each fovea.
99. - The eyes converge when object is more closer, and diverge when objects its moreaway – this is called vergence system.- Optokinetic movements: are the result of the integration of apparent movements of astationary external visual field relative to movement of head. It is the reflex that givesthe impression that you are moving backwards, even when stationary, when somethingnext to you moves forward. • Oculomotor control systems: Α) Vestibulo-ocular and opto-kinetic (systems) pathways: coordination of eye movement with movement of head. - Vestibule-ocular pathways: adaptive system, vestibular information for stabilization of picture. - Opto-kinetic pathways: stabilization of picture on fovea centralis by registration of object movement with visual system. Β) Slow pursuit system: adaptation of eye and object movements C) Vergent movements: botth eyes remain upon an object from different posi-tions.96 – Describe pathways for mydriatic papillary reflex. The axons of sympathetic preganglionic neurons, which are located in the IMLat the T1 level, synapse on neurons in the superior cervical ganglia. The postganglionicsympathetic fibers arising from the latter innervate the radial smooth muscle fibers of
100. the iris. Activation of the sympathetic nervous system results in contraction of the radialmuscles of the iris, which causes mydriasis (pupillary dilation). Functions of the Sympathetic Nervous System This division of the autonomic nervous system is activated in stressful situations.Thus, activation of the sympathetic nervous system results in an increase in blood flowin the skeletal muscles; an increase in heart rate, blood pressure, and blood sugar level;and pupillary dilation (mydriasis). These effects are widespread because one sympathet-ic preganglionic axon innervates several postganglionic neurons. All of these responsesprepare the individual for fight ﾝ or flight. ﾝ For example, in the need for flight, an in-crease in blood flow in the skeletal muscles will help in running away from the site ofdanger. In the need for fight, an increase in heart rate and blood pressure will help inbetter perfusion of different organs; an increase in blood sugar will provide energy; andpupillary dilation will provide better vision. The effects of simultaneous activation ofthe parasympathetic division of the autonomic nervous system (described later) comple-ment the effects of sympathetic stimulation.97 – Describe pathways for miotic papillary reflex. The axons of the parasympathetic preganglionic neurons located in the Edinger-Westphal nucleus (parasympathetic nucleus of the oculomotor nerve) leave the brain-stem through the oculomotor nerve (CN III) and synapse on the parasympathetic post-ganglionic neurons in the ciliary ganglion that is located in the orbit. The postganglionic
101. fibers from the ciliary ganglion enter the eyeball and innervate the circular (sphincter)smooth muscle fibers of the iris (Fig. 22-3A) and the circumferential muscles of the cil-iary body. When the parasympathetic innervation to the eye is activated, the circularmuscles of the pupil and the circumferential muscles of the ciliary body contract. Con-traction of circular muscles of the iris causes miosis (constriction of the pupil). Contrac-tion of circumferential muscles of the ciliary body results in the relaxation of the sus-pensory ligaments of the lens. The lens becomes more convex, thus allowing for greaterrefraction of the light rays, which is more suitable for near vision. These two responses(i.e., constriction of the pupil and making the lens more convex) are includeed in the ac-commodation reflex. 100 – Control of locomotion. At spinal level: Programmed in the spinal cord are local patterns of movement for all muscle ar-eas of the body – for instance, programmed withdrawl reflexes that pull any part of thebody away from the source of pain. The cord is the locus also of complex patterns ofthythmical motions such as to-and-fro movement of the limbs for walking, plus recipro-
102. cal motions on opposite sides of the body or of the hindlimbs versus the forelimbd infour-legged animals. Hindbrain level: The hindbrain provides two major functions for general motor control of thebody: 1) maintenance of axial tone of the body for the purpose of standing 2) continuos modification of the degrees of tone in the different muscles in response to information from the vestibular apparatuses for the purpose of maintaining body equilibrium. Motor cortex level: The motor cortex system provides most of the activating motor signals to the spinal cord. It functions partly by issuing sequential and parallel commands that set into motion various cord patterns of motor action. It can also change the in- tensities of the different patterns or modify their timing or other characteristics. When needed, the corticospinal system can bypass the cord patterns, replacing them with higher levels patterns from the brain stem or cerebral cortex. Associated functions of the cerebellum: the cerebellum functions with all lev-els of muscle control. It functions with the spinal cord especially to enhance the stretchreflex, so that when a contracting muscle encounters an unexpectedly heavy load, a longstretch reflex signal trasmitted all the way through the cerebellum and back again to thecord strongly enhances the load-resisting effect of the basic stretch reflex. Associated functions of the basal ganglia: the basal ganglia are essential tomotor control. Their most important functions are: 1. To help the cortex execute subconscious but learned patterns of movement. 2. to help plan multiple parallel and sequential patterns of movement that the mind must put together to accomplish a purposeful task.102 – Role of basal ganglia in motor control. Basal ganglia consist of the neostriatum (caudate nucleus and putamen),paleostriatum (globus pallidus), and two additional nuclei, the subthalamic nucleus andsubstantia nigra, which are included with the basal ganglia because of their anatomicalconnections (made with different nuclei of the basal ganglia) (Fig. 20-2). The primaryregions of the basal ganglia that serve as afferents (receiving areas) are the caudatenucleus and putamen. The major outputs of the basal ganglia arise from neurons located
103. in the medial pallidal segment. These neurons give rise to two fiber bundles, the ansalenticularis and lenticular fasciculus, which supply thalamic nuclei The efferent neurons of the internal globus pallidus and substantia nigrapars reticulata together give rise to the major pathways that link the basalganglia with upper motor neurons located in the cortex and in the brainstem . Thepathway to the cortex arises primarily in the internalglobus pallidus and reaches the motor cortex after a relay in the ventralanterior and ventral lateral nuclei of the dorsal thalamus. These thalamicnuclei project directly to motor areas of the cortex, thus completing a vastloop that originates in multiple cortical areas and terminates (after relays inthe basal ganglia and thalamus) back in the motor areas of the frontal lobe.In contrast, the axons from substantia nigra pars reticulata synapse on uppermotor neurons in the superior colliculus that command eye movements,without an intervening relay in the thalamus. This difference between the globuspallidus and substantia nigra parsreticulata is not absolute, however, since many reticulata axons also projectto the thalamus where they contact relay neurons that project to the frontaleye fields of the premotor cortex.Because the efferent cells of both the globus pallidus and substantia nigrapars reticulata are GABAergic, the main output of the basal ganglia isinhibitory. In contrast to the quiescent medium spiny neurons, the neurons inboth theseoutput zones have high levels of spontaneous activity that tend toprevent unwanted movements by tonically inhibiting cells in the superior103 – Disease of basal ganglia in humans-motor consequences. The circuitry in the basal ganglia suggests the presence of a highly sophisticatedand delicate set of functional mechanisms that are present within the basal ganglia forthe regulation of motor functions. Thus, any disruption of a component of these mecha-nisms, such as the balance between direct and indirect pathways, will result in signifi-cant changes in the signals transmitted to motor regions of the cerebral cortex.
104. Such changes are likely to result in compensatory response mechanisms withinthe overall circuitry, which will manifest as several kinds of movement disorders. Thesedisorders include involuntary movements during periods of rest (called dyskinesia),slowness of movement (called bradykinesia), or even a lack of movement (called akine-sia). In certain disorders, motor activity is also characterized by hypertonia or rigidity. Hypokinetic: hypokinetic disorders involve impaired initiation of movement,bradykinesia, and increased muscle tone. They are accounted for, in part, by the loss ofdopamine inputs into the part of the striatum that (1) excites the direct pathway throughD1 receptors and (2) inhibits the indirect pathway through D2 receptorsIn contrast, hyperkinetic disorders involve excessive motor activity characterized bymarked involuntary movements and decreased muscle tone. These disorders are ac-counted for by a diminished output through the indirect pathway to the external pallidalsegment.Parkinsons Disease Parkinsons disease is characterized by a variety of symptoms. The patient dis-plays involuntary movements at rest. The movements are typically rhythmic tremors atapproximately 3 to 6/sec, often appearing as a pill-rolling tremor involving the fingers,hands, and arm. Interestingly enough, the tremor disappears when the patient begins avoluntary movement.Chorea (Huntingtons Disease)In general, Chorea is characterized by wild, uncontrolled movements of the distal mus-culature, which appear as abrupt and jerky. Huntingtons disease is an inherited autoso-mal dominant illness with the genetic defect located on the short arm of chromosome 4.The gene encodes a protein referred to as huntingtin. In the mutated form, it includes amuch longer patch (than normal protein) of glutamine residues. Specifically, the DNAsegment (CAG) that encodes glutamine is repeated more than 60 times in the mutatedgene as opposed to approximately 20 repeats in the normal gene. Although it is not clearhow the mutant gene causes cell death, one hypothesis is that the Huntington proteincauses an induction of apoptosis in the nucleus of the cell. Perhaps this occurs by the al-teration of protein folding due to the increased amounts of glutamines, causing dysfunc-tion and ultimately the death of the cell. Degeneration is quite extensive. It involves the neostriatum, where there is sig-nificant loss of G104 – Role of the cerebellum in motor control. The cerebellum is concerned with at least three major functions. The first func-tion is an association with movements that are properly grouped for the performance ofselective responses that require specific adjustments. This is also referred to as synergyof movement. The second function includes the maintenance of upright posture with re-spect to ones position in space. The third function concerns the maintenance of the ten-sion or firmness (i.e., tone) of the muscle.
105. To complete even the simplest movements, such as walking or lifting a fork toones mouth, it would be apparent that they are indeed complex acts. To be able tocomplete either of these responses, the following elements are required:(1) contraction of a given muscle group or groups of muscles;(2) simultaneous relaxation of antagonist set(s) of muscles;(3) specific level of muscle contraction for a precise duration of time; and(4) the appropriate sequencing of contraction and relaxation of the muscle groupsrequired for the movement in question. The cerebellum determines the numbers of muscle fibers activated anddetermines the extent of the muscle contraction. In turn, the numbers of muscle fibersthat contract at a given time (i.e., the force or strength of contraction) are a function ofthe numbers of alpha motor neurons that are activated. The duration of contraction isdetermined, to a large extent, by the duration of activation of the nerve fibers thatinnervate the muscles required for the specific act. The cerebellum is responsible for precise and effective execution of purposefulmovements as well as the presence of appropriate posture in association with standingand with movement, and integrates and organizes the sequence of events associatedwith the response. Cerebellum should be able to both receive inputs from all the regionsof the central nervous system (CNS) associated with motor function and, consequently,send feedback responses back to these regions. Thus, such a region must function as acomputer does, to integrate sensory and motor signals, and consequently, it must havethe necessary computer-like or integrative properties for analysis of the afferent signalsand possess the reciprocal connections to form a series of feedback pathways to its af-ferent sources. The cerebellum receives inputs from all regions of the CNS associated withmotor functions and sensory regions mediating signals about the status of a givenmuscle or groups of muscles. It also has the capacity to send back messages to each ofthese regions. Moreover, the cerebellum possesses the machinery for integrating each ofthese afferent signals. As expected for a structure that monitors and regulates motor behavior, neuronalactivity in the cerebellum changes continually during the course of a movement. For in-stance, the execution of a relatively simple task like flipping the wrist back and forthelicits a dynamic pattern of activity in both the Purkinje cells and the deep cerebellarnuclear cells that closely follows the ongoing movement. Both types of cells are tonical-ly active a rest and change their frequency of firing as movements occur. The neuronsrespond selectively to various aspects of movement, including extension or contractionof specific muscles, the position of the joints, and the direction of the next movementthat will occur. All this information is therefore encoded by changes in the firing fre-quency of Purkinje cells and deep cerebellar nuclear cells.105 – Effects of cerebellar lesions on motor functions. The significance of the feedback pathways for motor functions is most appropri-ately understood when considered with respect to disorders of the cerebellum. Whenone or more of the feedback mechanisms are disrupted, a disorder of movement on theside of the body ipsilateral to the lesion emerges. The two types of such cerebellar dis-orders that have been described include ataxia (i.e., errors in the range, rate, force, and
106. direction of movement resulting in loss of muscle coordination in producing smoothmovements) and hypotonia (i.e., diminution of muscle tone). Ataxia There are a number of disorders that include ataxic movements. In particular,loss of coordination (called asynergy) is quite frequent with patients who have incurredcerebellar lesions. The components of complex movements occur as a series of simpleindividual movements (called decomposition of movement). The patient may also notbe able to accurately move his hand in space. For example, if the patient is asked tomove his hand to touch his nose, he will either undershoot or overshoot the mark. Thisdisorder is called dysmetria. Alternatively, the patient may be unable to make rapid al-ternating rotational movements of her hand. This disorder is called dysdiadochokinesia.As the patient voluntarily attempts to move her limb, she may display a tremor, which iscalled an intention tremor. All of these disorders most frequently involve the cerebellarhemispheres and presumably reflect a disruption of the feedback circuit between thecerebellar cortex and the cerebral cortex that governs movements of the distal muscula-ture.HypotoniaHypotonia has been associated with damage to parts of the cerebellar cortex, but thespecific regions have not been clearly identified. It has been suggested that lesions, pos-sibly of the paravermal region or hemisphere of the posterior lobe, are linked to this dis-order. The precise mechanism underlying this disorder remains unknown. Because theoutputs of the cerebellum to a brainstem structure, such as the lateral vestibular nucleus(which excites extensor motor neurons), are typically excitatory, such a lesion maycause loss of excitation to the lateral vestibular nucleus (from the fastigial nucleus), re-sulting in loss of excitatory input to the spinal cord motor neurons and subsequent hypo-tonia.Cerebellar Nystagmus and Gait Ataxia Lesions of the vermal region of the cerebellar cortex or fastigial nucleus can re-sult in nystagmus. Presumably, the effect is due to a disruption of the inputs into themedial longitudinal fasciculus from vestibular nuclei. This is likely caused by the lossof or change in inputs into the vestibular nuclei from the fastigial nucleus because of thelesion in the fastigial nucleus or cerebellar cortical regions that project to the fastigialnucleus.106 – Describe structural arrangement on the enteric nervous system. The enteric division consists of neurons in the wall of the gut that regulategastrointestinal motility and secretion. The enteric system consists of two layers ofneurons that are present in the smooth muscle of the gut: the myenteric (Auerbachs)and submucosal (Meissners) plexuses. The neurons of the myenteric (Auerbachs)
107. plexus control gastrointestinal motility, while the neurons of the submucosal(Meissners) plexus control water and ion movement across the intestinal epithelium.Excitatory transmitters of motor neurons and interneurons in the smooth muscle of theGIT are probably acetylcholine and substance P. The enteric nervous system isintrinsically active. The enteric system is also controlled by sympathetic and parasympatheticinnervation (extrinsic innervation). The sympathetic innervation is derived from branches of thoracic, lumbar, andsacral sympathetic chains. Most of the sympathetic fibers of the extrinsic innervationare postganglionic. The parasympathetic innervation is derived from the vagus and pelvic nerves.Most of the parasympathetic fibers of the extrinsic innervation are preganglionic. Theextrinsic system can override the intrinsic system when the sympathetic orparasympathetic nervous system is activated.107 – Describe connections of the CNS that control autonomic nervous system. Central autonomic control circuits coordinate autonomic functions and theongoing behavioral needs of the organism through the activities of the somatomotor,endocrine, and autonomic systems. These systems are represented in overlappingregions of the brain. The behavioral strategies and reflex mechanisms within these
108. circuits act in the defense of the organism and in homeostasis, which are coordinated byinterconnected groups of nuclei in the brainstem and higher forebrain centers. Three of the key components of the central autonomic control circuits are the 2. solitary nucleus: the solitary nucleus is the major recipient of visceral afferent inputs including taste. Afferent information is, in turn, utilized to modulate several autonomic functions such as cardiovascular reflexes 3. hypothalamus, which is the most important neural center in the overall control of visceral and endocrine functions. he hypothalamus is the master visceral control center in the regulation of many autonomic and endocrine responses and in homeostasis 4. rostral ventrolateral reticular nucleus (n RVL), a major relay motor nucleus regulating the autonomic nervous system. The adrenergic nRVL regulates autonomic responses (1) via projections both to the preganglionic neurons of the dorsal motor nucleus of the vagus of the parasympathetic system and to the preganglionic neurons of the intermediolateral nuclei of the sympathetic system and (2) via rostral projections to higher centers of the brain through the periventricular and the tegmental tracts of the brainstem. The nuclei forming the extensive central autonomic control network within thebrainstem and forebrain are linked together and integrated by two bidirectionalpathways: the (trans)tegmental tract within the reticular formation and theperiventricular tract within the central gray matter. The core nuclei of this networkcomprise the parabrachial nucleus and the periaqueductal gray of the brainstem, thehypothalamus, the amygdala of the limbic system, the visceral sensory thalamic nuclei,and visceral areas of the cerebral cortex. Critical modulating influences on the centralautonomic network are made by brainstem noradrenergic cell groups (e.g., A1),adrenergic cell groups (e.g., C1 and C3), serotonergic raphe nuclei, and interneuronswithin the nRVL. These central autonomic control circuits are functionally endogenous.The basic performance of their roles can be performed in the absence of hypothalamiccontrol. The solitary nucleus receives afferent fibers from visceral receptors located inthe taste buds, carotid body, carotid sinus, and many other locations associated withinthe array of visceral organs. The solitary nucleus and its relay nRVL send outputs toautonomic circuits via two general routes: One is a focused relatively simple reflexcircuitry and the second is a multidimensional complex circuitry. In the first,information is directed locally into lower brainstem visceral circuits such as thecardiovascular and respiratory centers. In the second, information is directed to themore extensive and complex circuitry of the upper brainstem and forebrain componentsof the central autonomic control network. The latter is integrated into behavioralresponses associated, for example, with the limbic system. The central autonomic control nuclei and centers are interconnected by thetegmental tract and periventricular tract to and from the parabrachial nucleus,periaqueductal gray, and such forebrain structures as the hypothalamus, amygdala,visceral sensory centers, and areas of the thalamus and neocortex. In addition, neuralinterconnections between these structures result in interactions directed to thehypothalamus. Visceral sensory information derived from the solitary nucleus is relayed
109. to the parabrachial nucleus, which acts as a key brainstem processor projecting to andreceiving communications from the periaqueductal gray and forebrain centers. Theparabrachial nucleus has a functional role in behavioral responses to various visceralsensations including taste as is indicated by the prevention of previously conditionedbehavioral responses to gustatory cues in rodents following its destruction. The periaqueductal gray is a processor. (1) Its projections to the lateral tegmental receptive field (LTF) of the medullamodulate actions associated with changes in blood pressure and heart rate throughcardiovascular reflexes. The resulting “fight or flight” response results in reducing theamount of blood flow directed to the viscera and increasing blood flow to the lowerextremities to enhance sustained runningbehaviors. (2) Its projections to the substantia nigra and the extrapyramidal system result inthe agonizing facial contortions of a marathon runner during the last miles of a race.The amygdala of the limbic system is involved in many autonomic responses withspecific behaviors.. This amygdaloid nucleus projects to the hypothalamus and thelateral tegmental field (LTF) in the medulla.108 – Chemical transmission at autonomic junctions. Neurotransmitters in the Autonomic Nervous System Preganglionic Terminals
110. Within the autonomic ganglia, acetylcholine is the transmitter released at theterminals of the sympathetic and parasympathetic preganglionic fibers. The terminalbranches of the preganglionic fibers contain vesicles enclosing the neurotransmitter.The terminals make synaptic contacts with the postganglionic neurons located in theganglia. Postganglionic Terminals The terminals of the sympathetic and parasympathetic postganglionic neuronsinnervate the effector cells in the target organs. At the terminals of most sympatheticpostganglionic neurons, norepinephrine is the transmitter, with the exception of thoseneurons innervating sweat glands and blood vessels of the skeletal muscles, whereacetylcholine is the neurotransmitter. At the terminals of all the parasympatheticpostganglionic neurons, acetylcholine is the neurotransmitter. Acetylcholine liberated in the synaptic cleft is removed by acetylcholinesterasethat hydrolyzes the transmitter. Acetylcholinesterase inhibitors are used clinically in thetreatment of many diseases. Receptors: Cholinergic Receptors These receptors have been divided into two main classes: cholinergic muscarinicand nicotinic receptors. Cholinergic receptors located in the visceral effector organ cells(smooth and cardiac muscle and exocrine glands) are called cholinergic muscarinicreceptors. Responses elicited by the stimulation of these receptors in the visceraleffector organs, called muscarinic effects of acetylcholine, include decrease in heartrate, miosis, and secretions of different glands (lacrimal, salivary, and sweat glands andglands in the GIT). Cholinergic receptors located in the adrenal medulla and autonomicganglia are called nicotinic receptors. Acetylcholine is the transmitter at thepreganglionic terminals synapsing on epinephrine- and norepinephrine-secreting cells ofthe adrenal medulla.Adrenergic Receptors Adrenergic receptors are divided into two major classes: alpha- and beta-adrenergic receptors. These classes have been further subdivided into alpha1- andalpha2-adrenergic receptors and beta1- and beta2-adrenergic receptors.
111. Alpha1-adrenergic receptors are located on the membranes of postsynaptic cells.These receptors may be linked through a G-protein. G-proteins bind guanosinediphosphate (GDP) and guanosine triphosphate (GTP). When norepinephrine binds toan alpha1-adrenergic receptor, the receptor is activated, and second messengers inositol 2+1,4,5-triphosphate (IP3) and diacylglycerol (DAG) are liberated. IP3 releases Ca fromits stores in the endoplasmic reticulum and is also phosphorylated to form inositol1,3,4,5-tetraphosphate (IP4), which opens calcium channels located in the cell 2+membrane. Ca then binds with calmodulin, and phosphorylation of a protein occurs toelicit a cellular response. DAG activates protein kinase C, which, in turn, promotesprotein phosphorylation and subsequent cellular response. Alpha2-adrenergic receptors are present on the presynaptic membranes ofadrenergic nerve terminals. Activation of alpha2-adrenergic receptors at these endingsby the released transmitter (norepinephrine) inhibits further release of the transmitter.This phenomenon is called autoinhibition. Stimulation of alpha2-adrenergic receptorshas been reported to inhibit adenylate cyclase and lower cyclic adenosinemonophosphate (cAMP) levels in some effector cells. cAMP stimulates enzymes (e.g.,protein kinase A), which then phosphorylate appropriate ion channels. Phosphorylationof ion channels by protein kinases results in the opening of these channels, ions flowacross the cell membrane, and the cells are depolarized and rendered more excitable.Decrease in cAMP levels, therefore, elicits opposite responses. Beta1-adrenergic receptors are located in the heart; stimulation of these receptorsresults in an increase in heart rate and contractility. Beta2-adrenergic receptors are located in smooth muscles (e.g., bronchialsmooth muscle); their activation results in the relaxation of these muscles.110 – Control of feeding behavior. Feeding and ingestive behaviors are clearly regulated by the hypothalamus. Tworegions, the medial and lateral hypothalamus, play key roles in the regulation of feeding
112. responses. Stimulation of the lateral hypothalamus has been shown to induce feedingbehavior, while stimulation of the medial hypothalamus suppresses this behavior.Moreover, lesions of the lateral hypothalamus induce aphagia, while lesions of themedial hypothalamus result in hyperphagia. Based on such evidence, the lateralhypothalamus has often been referred to as a feeding center, while the ventromedialhypothalamus has been called a satiety center. It appears that a number of different mechanisms may be operative within thesehypothalamic nuclei. The ventromedial nucleus appears to play a critical role here, thisnucleus responds to changes in caloric intake. There is believed to be a set-pointgoverning hypothalamic regulation of food intake. The set-point is governed by suchfactors as metabolic rate of the organism, immediate past history of food intake, andpresent level of food intake. Lesions of the medial hypothalamus disrupt this set-point,leading to large increases in food intake and weight gain. The ventromedialhypothalamus and adjoining nuclei have been linked to several neurotransmitter andhormonal systems. For example, inhibition of feeding behavior occurs afteradministration of CCK to the paraventricular region. Part of the satiety mechanisminvolves a release of CCK from the medial hypothalamus following food intake. Othercompounds associated with the medial hypothalamus, such as glucagon andneurotensin, have similar functions. Thus, lesions of the medial hypothalamus mayresult in hyperphagia because of disruption of these compounds and may affect therelease of other hormones, such as ACTH and insulin, that normally regulate metabolicrates. Several mechanisms may also be operative with respect to food intake functionsinvolving several nuclei of the hypothalamus. Sensory processes play an important rolein feeding behavior. Of particular significance are the learned sensory cues associatedwith olfaction and taste. These signals, which intensify the drive for food, involve sig-nals that reach the amygdala, which, in turn, are relayed to the lateral hypothalamus viathe ventral amygdalofugal pathway. The loss of motivation for food following lesions ofthe lateral hypothalamus may be related, in part, to the disruption of inputs to the lateralhypothalamus from the amygdala triggered by sensory signals associated with food.In addition to the lateral hypothalamus, the paraventricular nucleus also appears to con-tribute to feeding behavior. Several different peptides (galanin, neuropeptide Y, andopioids) and norepinephrine can induce feeding responses in rats when microinjectedinto the paraventricular nucleus.111 – Control of fluid intake.The hypothalamus regulates body water by 2 mechanisms: 1. by creating the sesation of thirst, which makes one drink water.
113. 2. by controlling the excretion of water in urine. An area called the thirst center is located in the lateral hypothalamus. When theeletrolytes levels inside the neurons either of this center or neighbouring areas of thehypothalamus become too concentrated, onde develops an intense desire to drink water,one will seaken out to the nearest sorce of water and thus drink fluids to return theelerolyte concentration of the thirst neurons back to normal. Stimuli for thirst: • increase osmolality via osmoreceptors in anterior hypothalamus • decrease of extracellular fluid volume that leads to an increase in renin levels leading to an increase in angiotensin II. • Decrease of blood volume, decrease in blood pressure (neural information from baroreceptors). • Increase in angiotensin II, acts on the subfornical organ and organum vascolusum. • Dryness of pharyngeal mucous membrane. • Physochological and social factors • Mouth dryness Control of renal excretion of water is mediated mainly in the supraoptic nucleus.When the fluids become too concentrated, the neurons become stimulated. The nervefibers from these neurons project downwards thruths the fundibulum of thehypothalamus into the posterior pituitary gland, where nerve endings secrete ADH. ADH produces its major effects by increasing water absorption in the kidneys. ADHrelease is triggered by two factors: (1) neuronal impulses from afferent sources of the supraoptic nucleus (frequentlyoccurring in response to sudden increases in emotional states); (2) the sensory properties of supraoptic nuclei that enable them to sense changes inblood osmolarity. In this sense, the supraoptic and paraventricular nuclei serve as osmoreceptors.Under conditions in which there is an increase in osmotic pressure resulting from suchfactors as reduced fluid intake, increased amount of salt intake, or fluid loss due todiarrhea or sweating, supraoptic neurons discharge more rapidly and release increasedamounts of ADH into the vascular system. The primary target of ADH is the distalconvoluted tubules of the kidney. The mechanism of action of ADH hormone is asfollows: when the plasma concentration of salt increases, the osmotic pressure increaseswithin the arterial blood vessels that supply the hypothalamus. This results in anincrease in production and release of ADH, which acts on its target organ, the distalconvoluted tubule, causing reabsorption of excess water, thus allowing the blood to re-establish osmolality. Damage to the posterior pituitary or the pituitary stalk produces acondition in which there is an excess of excretion of low-gravity urine. This condition isreferred to as diabetes insipidus and results from loss of secretion of ADH.
114. So we can resume the processes of fluid intake in two main points: • include the role of the paraventricular nucleus in releasing ADH in response to increases in tissue osmolarity • the role of the subfornical organ in responding to the presence of angiotensin II by exciting neurons in the anterior hypothalamus and preoptic region. stimulation of the paraventricular nucleus activates a mechanism that induces water retention from the kidneys. • A separate mechanism has also been described: activation of the tissue surrounding the anteroventral aspect of the third ventricle, which includes the preoptic region, is believed to excite a process that induces the behavioral process of drinking.112 – Temperature regulation – physiological and behavioral components. Temperature Regulation
115. Temperature regulation requires the integration of a number of processes associ-ated with hypothalamic functions. These include: (1) activation of temperature-sensitive neurons (thermoreceptors) that canrespond to increases or decreases in blood temperature; (2) the capacity of the hypothalamus to activate thyroid-releasing hormone,which leads to secretion of TSH, with subsequent secretion of thyroid hormone for in-creases in metabolic rates; (3) activation of autonomic mechanisms, which, in turn, dilate or constrict pe-ripheral blood vessels that serve to cause loss or conservation of body temperature, re-spectively; and (4) activation of behavioral responses such as panting (to generate heat loss)and shivering (to conserve heat). Body temperature normally remains relatively konstant (36,6 ± 0,6) is the resultof a balance between neuronal mechanisms subserving heat loss and heat conservation.A group of neurons situated in the anterior hypothalamus-preoptic region responds tochanges in blood temperature. These neurons are specifically designed to prevent bodytemperature from rising above set values. When body temperature does increase, anteri-or hypothalamic neurons discharge, and efferent volleys are conducted down their ax-ons to respiratory and cardiovascular neuronal groups of the lower brainstem and spinalcord. The net effect of such activation is initiation of vasodilation and perspiration, lead-ing to heat loss. Therefore, this region of the hypothalamus is often referred to as a heatloss center. Moreover, neurons in this region respond to substances called pyrogens(which cause marked increases in body temperature) by discharging in an attempt to re-establish normal body temperature. In addition, certain neurons in this region, as well asin adjoining regions of the septal area that contain vasopressin, are capable of counter-acting the actions of pyrogens. Accordingly, this group of neurons is referred to as anantipyrogenic region. Temperature receptors: Skin: more cold than warmth receptors. Causes shivering, skin vasoconstrictionand inhibit sweating Deep temperature receptors: especially in spinal cord, abdomen, viscera andaround great veins. Also detect cold rather than warmth. 113 – Control of sexual behavior. Sexual Behavior Female sexual behavior is directly dependent on the relationship between en-docrine function, the presence of hormonal-neural interactions, and activation of neural
116. circuits that govern the elicitation of species-specific sexual responses. One of the keystructures controlling sexual behavior is the ventromedial hypothalamus. It contains es-trogen and progesterone receptors. Stimulation of the ventromedial nucleus by chemi-cals (i.e.,cholinergic stimulation) induces a sexual response referred to as lordosis. Thisresponse is characterized by arching of the back (by the female) coupled with a rigidposture and a deflection of the tail, all of which allows intromission by the male. In con-trast, lesions of the ventromedial nucleus significantly reduce sexual behavior. The correlation between sexual behavior and estrogen levels is quite high.Therefore, it is reasonable to conclude that increased levels of estrogen act on estrogenreceptors within the ventromedial hypothalamus to trigger a neural mechanism that ex-cites other neurons in lower regions of the central nervous system, such as the midbrainPAG and spinal cord, which serve to induce the expression of sexual behavior. Progesterone also likely acts on ventromedial neurons, the net effect of whichis to intensify the sexual response to estrogen. Lordosis reaction is also modulated bymonoaminergic inputs and acetylcholine. In particular, lordosis behavior is enhanced bynorepinephrine, suppressed by serotonin, and induced by acetylcholine when each of theagonists for these transmitters is microinjected directly into the ventromedial hypothala-mus. Part of the overall hypothalamic mechanism underlying sexual behavior may in-volve the release of GnRH from the anterior hypothalamus (preoptic region). Theseneurons project to the median eminence, where the peptide is released into the portalcirculation. The peptide is then transported to the anterior pituitary, resulting in increas-es in estrogen levels. In addition, the gonadotropin pathway from the anterior hypotha-lamus also reaches the midbrain PAG, where the release of gonadotropin-releasing hor-mone can induce lordosis. It is reasonable to conclude that all of these mechanismscome into play when sexual behavior occurs normally in humans. Ovarectomy does not reduce the libido or sexual ability, post-menopausal wom-en continue to have sexual ability due to steroid from the afrenal cortex which are con-verted to estrogen. Male sexual behavior is induced or augmented by the presence of testosterone.Testosterone appears to act on the preoptic region to produce the various behavioralcharacteristics of sexual behavior. This suggests that the preoptic region plays an impor-tant role in sexual behavior in both males and females. It is of interest to note that themorphological appearance of the preoptic region differs between males and females,and the appearance is dependent on the extent of release of LH from the anterior pitu-itary. For this reason, the preoptic region contains the sexually dimorphic nucleus,which is a somewhat rounded, compact structure that is larger in males than females. Itmay be that the kind of morphology present in the preoptic region may provide the neu-ral substrate for the kind of sexual behavior that is expressed by a given organism. Likethe female, male sexual responses are modulated by various neurotransmitters, such asdopamine, and by neuropeptides (gonadotropin-releasing hormone, substance P, andneuropeptide Y).114 – Sexual differentiation of the brain.
117. In females animals, exposure to sex steroids in utero during early postnatal lifecause maked abnormalities of sexual behavious. In female rats treated with small amount of androgens before the 5th day of life donot have normal heat periods when they nature ad they do not shoe the cyclic release ofpituitary gonadotropins characteristic of the adult female but rather, the tonic, szteadysecretion characteristic of the adult male-their brains have been masculized by the singleexposure to androgens. In female monkeys exposed to androgen in utero do not lose female pattern of gon-adrotopin secretion but do develop abnormalities of sexual behaviour in adulthood. Exposure of human females to androgens in utero does not change cyclic pattern ofhormone release, however masculinizing effects on behaviour do occur. Male rats which are castrated at birth develop the female pattern of cyclic gonadro-topin release and show female sexual behaviour when given small doses of ovarian hor-mones. Androgens have no effect on normal males. Development of female hypothalamusdepends on the absence of androgens in cyclic life, not on the exposure to female hor-mones.115 – Central system of emotion and stress – major strctures and pathways.
118. James Papez described a cicuit that he suggested to form the anatomical site foremotion. Consisted of: -hypothalamus. - mamillary bodies. - anterior thalamic nuclei. - cingulate gyrus. - hippocampal formation. This circuit has been enlarged to include: - septal area - nucleus accumbens - neocortical areas (includding amygdala and orbitofrontal cortex). The connectng pathways of the system are the: - alveus - fimbria - fornix - mammilothalamic tract According to this hypothesis, the hypothalamus feeds emotional to cingulate gyrusthrough the mamillary bodies and the mamillothalamic tract via the anterior thalamicnuclei. The cortex in turn modulates hypothalamic function through hippocampal form-ation, which processes information and communicates it to the hypothalamus via thefornix.116 – Sensory afferents to the limbic forebrain. • From entorrhinal cortex (a 25)
119. - its gray matter is connected to the gray matter of the hippocampus via thesubiculum. -it receives sensory information from a variety of cortices, e.g. eye, nose • From amygdala - receives sensory information from all portions of the limbic cortex, neocortex (oftemporal, parietal, occipital, auditory and visual areas). - amygdala send signals into the hippocampus, thalamus, hypothalamus andseptum. - involved in emotion and memory Relatively few limbic regions receive direct sensory inputs, amygdala is the onlystructure receiving afferents from cortical, thalamic exteroreceptive and subcortical vis-ceral systems. The amygdala is situated well to play a key role in emotional functions. Entorrhinal cortex is the princupal source of inputs to the hippocampus. If theentorrhinal cortex received only olfactory inputs, this would not be very impressive, butit also receives projections from the cingulate gyrus (via cingulum), from the orbitalcortex (via the uncinate fasciculus) and from the amygdala and other areas of temporallobe. Through these additional connections the hippocampus has acess to virtually alltypes of sensory information. In addtition, some septal and hypothalamic fibers reachfrom the contralateral hippocampus by passing from one crus of the fornix to the otherbeneath the splenicum of the corpus callosum in the hippocampal comissure. Amygdala receives a great deal of sensory input in a highly processed form. Singleamygdalar cells may be selective or my respond to a various combination of many dif-ferent sensory modalities, including somatosensory, visual, auditory and all types of vis-ceral inputs. The afferents carrying this information arrise in several locations and reachthe amygdala by traveling in the reverse direction along the paths followed by amygdalaefferents.117 – Projections of the limbic forebrain to effector systems The fornix connects the hippocampus to the mamillary bodies, which are in turnconnected to the anterior nuclei of the thalamus by the mamillo-thalamic tract. The an-
120. terior nuclei of the thalamus project to the cingulate cortex and from there, connectionsto the hippocampus complete a complex closed circuit also known as Papez circuit. The lateral and paraventricular nuclei of the hypothalamus receive aferents fromwidespread areas of the limbic forebrain and project to the sympathetic regions of themedulla oblongata and apinal cord. Connection between the limbic forebrain and parasympathetic output pathways al-low parasympathetic activity to be modulated. In addition to autonomic activation, emotional arousal is typically accompanied byhormone secretion; the release of catecholamines is controlled by limbic projections. Limbic efferents to the medial basal region of the hypothalamus mediate the releaseof adenohypophyseal hormones. Also limbic forebrain efferents to the paraventricular and supraopticregion control the release of vasopressin and oxytocin. 119 – Declarative and non-declarative memory. Memory is an organisms mental ability to store, retain and recall information. Declarative memory is the aspect of human memory that stores facts. It is socalled because it refers to memories that can be consciously discussed, or declared. Itapplies to standard textbook learning and knowledge, as well as memories that can betravelled back to in ones minds eye.
121. Declarative memory is associated with consciousness and is dependent on thehippocampus and other parts of the medial temporal lobes of the brain for its retention.It may be divided into memory for events (episodic memory) and memory for words,rules and language (semantic memory).- semantic memory: Theoretical knowledge independent of time and place (e.g.knowing that an apple is called by society to be a "fruit"), a piece of data.- episodic memory: factual knowledge of a specific moment in time and place,personal experiences. Declarative memory initially required for activities such as bike riding canbecome non-declarative once the task is fully learned. Declarative memory and many forms of non-declarative memory involve: • Short-term memory: lasting seconds to hours, during which processing in the hippocampus and elsewhere lays down long-term changes in synaptic strength. Can be referred as the capacity for holding a small amount of information in mind in an active, readily available state for a short period of time. The duration of short-term memory is assumed to be in the order of seconds. Estimates of the capacity of short-term memory vary – from about 3 or 4 7±2 elements • Long-term memory: years and sometimes for life. Short-term memory is a temporary potentiation of neural connections that can become long-term memory through the process of rehearsal and meaningful association. Non-declarative memory:Non-declarative memory does not involve awareness orreflexive memory. Its retention does not involve processing in the hippocampus, at leastin most instances, and it includes among other things, skills, habits and conditionalreflexes each one is acquired, become unconscious and automatic. It also includespriming, which is facilitation of recognition of words or objects by prior exposure tothem, e.g. the improved recall of a word when presented with the first few letters of it. Other forms of non-declarative memory may be divided into non-associativeform (the organism learns about a single stimulus) and associative form (the organismlearns about the relation of one stimulus to another). Habituation: is a simple form of learning in which a neutral stimulus is repeatedmany times. The first time it is applied, it is novel and evokes a reaction (the orientingreflex or ´what is it´ response. However it evokes less and less electrical responses as itis repeated. Eventually the subject becomes habituated to the stimulus and ignoresit.Sensitization: is in a sense the opposite of habituation. A repeated stimulus producesa greater response if it is coupled one or more times with unpleasant stimuli. It iscommon knowledge that intensification of the arousal value of stimuli occurs in humans 120 – Cellular mechanisms of habituation and sensitization. Habituation and sensitization are both types of non-associative memory. Habituation: Its is a simple form of learning in which a neutral stimulus is repeated manytimes. The first time it is applied, it is novel and evokes a reaction (the orienting reflex
122. or ´what is it response´). However it evokes less and less electrical response as it isrepeated. Eventually, the subject becomes habituated to the stimulus and ignores it. In other words, habituation is when a stimulus is benign and is repeated over andover, the response to the stimulus gradually disappears. This is associated with lowrelease of neurotransmitters from the pre-synaptic terminal because of low intracellularCa++. The low intracellular concentration od Ca++ is due to gradual inactivation of Ca++ channels. It can be short-term, or it can be prolonged if exposure to the benignstimulus is repeated many times. Habituation need not be conscious - for example, a short time after a humandresses in clothing, the stimulus clothing creates disappears from our nervous systemsand we become unaware of it. In this way, habituation is used to ignore any continualstimulus, presumably because changes in stimulus level are normally far moreimportant than absolute levels of stimulation. This sort of habituation can occur throughneural adaptation in sensory nerves themselves and through negative feedback from thebrain to peripheral sensory organs. Habituation is frequently used in testing psychological phenomena. Both adultsand infants gaze lesser at a particular visual stimulus the longer it is presented. Theamount of time spent looking at a new stimulus after habituation to the initial stimulusindicates the effective similarity of the two stimuli. It is also used to discover theresolution of perceptual systems. For instance, by habituating someone to one stimulus,and then observing responses to similar ones, one can detect the smallest degree ofdifference that is detectable. Sensitization In a sense is the opposite of habituation. A repeated stimulus produces a greater response if it is coupled one or moretimes with an unpleasant/pleasant stimulus. His common knowledge that intensificationof the arousal value of stimuli occurs in humans. The mother who sleeps with manykind of noise but wakes promptly when her baby cries, for example. Therefore sensitization is the prolonged occurrence of augmented post-synapticresponse after a stimulus to which an animal has become habituated is paired once orseveral times with a noxious stimulus. Sensitization primarily refers to AMPA receptor-associated sensitization.However, there are others as well, e.g. sensitization in drug addiction.121 – Sleep-walking periodicity Sleep is divided into two broad types: Rapid Eye Movement (REM) and Non-Rapid Eye Movement (NREM) or "Non-REM" sleep. Each type has a distinct set ofassociated physiological, neurological and psychological features. Sleep proceeds in cycles of REM and the three stages of NREM, the ordernormally being:
123. Stages N1 -> N2 -> N3 -> N2 -> REM. In a typical night of sleep, a young adult first enters NREM phase, passesthrough stages I and II and spends 70-100min in stages III and IV. Sleep the lightens,and an REM period follows. This cycle is repeated at intervals of about 90min throughthe night. The cycles are similar, thought there is less stages III and IV and more REMsleep towards morning. Thus 4-6 REM periods occur per night. REM sleep occupying80% of total sleep time in premature infants and 60% in full term neonates. Thereafter,the proportion of REM sleep falls rapidly and plateaus at about 25% until it falls furtherin older age. Children have more total sleep time at stage IV than adults. Consciousnessis dependent on the interaction between the reticular information and thalamocorticalcircuits. Suprachiasmatic nucleus serves as the biological clock for the sleep-awakecycle. Sleep stages and other characteristics of sleep can be measured bypolysomnography in a sleep laboratory using among other tools electroencephalography(EEG) for brain waves, electrooculography (EOG) for eye movements andelectromyography (EMG) for activity of skeletal muscles. Criteria for REM sleep include not only rapid eye movements but also rapid lowvoltage EEG, commonly called brain waves. In mammals, at least, low muscle tone isalso seen, often called paralysis. Most memorable dreaming occurs in this stage. REMsleep accounts for 20–25% of total sleep time in normal human adults; NREM (non-REM) accounting for the rest. In NREM sleep, there is relatively little dreaming. Non-REM encompasses three stages; stage 1 (N1), stage 2 (N2), and stage 3 (N3); N3 beingreferred to as deep sleep or slow-wave sleep (SWS). Sleep stages are differentiated bybrain waves, eyes movements, and skeletal muscle activity. Sleep disorders:InsomniaFatal familiar insomniaNarcolepsy-episodic sudden loss of muscle toneSomnambulism – sleep-walkingSleep apnea.122 – Sleep cycles (non REM, REM) In mammals and birds, sleep is divided into two broad types: Rapid EyeMovement (REM) and Non-Rapid Eye Movement (NREM) or "Non-REM" sleep. Eachtype has a distinct set of associated physiological, neurological and psychologicalfeatures.Sleep proceeds in cycles of REM and the three stages of NREM, the ordernormally beingstages N1 -> N2 -> N3 -> N2 -> REM. Sleep is prompted by natural cy-cles of activity in the brain and consists of two basic states: rapid eye movement (REM)sleep and non-rapid eye movement (NREM) sleep, which consists of Stages 1 through
124. 4.During sleep, the body cycles between non-REM and REM sleep. Typically, peoplebegin the sleep cycle with a period of non-REM sleep followed by a very shortperiod of REM sleep. Dreams generally occur in the REM stage of sleep. non-REM sleep: The period of NREM sleep is made up of stages 1-4. Each stage can last from 5 to 15 minutes. A completed cycle of sleep consists of a progression from stages 1-4 before REM sleep is attained, then the cycle starts over again. 1.Stage 1: Polysomnography (sleep readings) shows a reduction in activity between wakefulness and stage 1 sleep. The eyes are closed during Stage 1 sleep. One can be awakened without difficulty, however, if aroused from this stage of sleep, a person may feel as if he or she has not slept. Stage 1 may last for five to 10 minutes. Many may notice the feeling of falling during this stage of sleep, which may cause a sudden muscle contraction (called hypnic myoclonia). 2.Stage 2: This is a period of light sleep during which polysomnographic readings show intermittent peaks and valleys, or positive and negative waves. These waves indicate spontaneous periods of muscle tone mixed with periods of muscle relaxation. The heart rate slows and the body temperature decreases. At this point, the body prepares to enter deep sleep. 3.Stages 3 and 4: These are deep sleep stages, with stage 4 being more intense than Stage 3. These stages are known as slow-wave, or delta, sleep. If aroused from sleep during these stages, a person may feel disoriented for a few minutes. REM sleep There is rapid eye movement sleep Has a duration of 5-30 minutes and occurs every 90 minutes. 4-6 REM´s per night Active dreaming and active body movements, but muscles are inhibited at this time. Large phasic potentials, in groups of 3-5, that originate in the pons and pass rapidly to the lateral geniculate body and from there to the occipital cortex- pontogeniculooccipito (PGO) spikes. Skeletal muscle tone in the neck is reduced. Rapid moving movements of the eye.123 – EEG, event related potentials. Electroencephalography (EEG) is the measurement of electrical activityproduced by the brain as recorded from electrodes placed on the scalp. The maindiagnostic application of EEG is for epilepsy but this technique is also used toinvestigate much other pathology such as sleep-related disorders, sensory deficits, braintumors, etc.
125. It measures potential differences between two active electrodes on the scalp orbetween a scalp electrode and an inactive electrode, which is usually placed behind theear. The EEG measures the summation of excitatory postsynaptic potentials (EPSPs)and inhibitory postsynaptic potentials (IPSPs) from the scalp. Because these signals arelow in amplitude, a differential amplifier is used to make the waves more visible. Goldor platinum electrodes are placed on the scalp after thorough cleaning with an abrasiveagent. The pins from the wire attached to the electrodes are plugged into a jackbox thatis attached by cable to the amplifier. There are many characteristic waveforms seen on both normal and abnormalEEGs. For instance, when a normal subject lies quietly, an alpha rhythm is found in theoccipital leads. This disappears with eye opening. If this rhythm is slow or absent, thenthere may be a neurologic problem. States of alertness are characterized by waves oflower amplitude and higher frequency. Similarly, epileptiform spikes are sharp wavesfollowed by a slow wave, and the presence of these entities is abnormal. If the patienthas had seizures or questionable seizures in the past, then the presence of epileptiformspikes will assist in making the diagnosis. Additionally, certain patterns, such as a 3-per-second spike and wave when the patient has had a history of staring spells, will as-sist in making the diagnosis of an absence seizure. Likewise, waves of 4 to 7 Hz record-ed over the temporal lobes or within the hippocampal formation, called a theta rhythm,reflect a dysfunction of hippocampal tissue in humans. In lower forms of animals, thetarhythms may appear normal when recorded from hippocampal tissue, especially duringconditions reflecting altered motivational states, such as when an animal is approachinga goal. Delta rhythms are defined as very slow, 1- to 3-Hz, synchronous waves that oc-cur under conditions of severe trauma to the brain (e.g., such as brain tumors). Theyalso occur normally for short periods during sleep. EEG is also useful in other disorders,such as coma.124 – Specialization of hemispheres Dominant hemisphere (categorical hemisphere) a) located on the left in 95 % of people
126. b) interpretative function of Wernicke´s area and angular gyrus as well as func-tions of motor and speech areas are highly develped in this hemisphere. c) almost all people who is left hemisphere is dominant are right handed because motor areas are dominant. d) promoter of speech (Broca´s area) is dominant on the left. At birth, left poste- rior temporal lobe is usually larger than right. e) Wermick´s area was first used to interpret language from hearing, then latter also the reading f) Lesion of categorical/dominant hemisphere produces language disorders such as dyslexia(much more common in left handed people) and aphasia. Non-dominant hemisphere (representative) a) is specialized in spatiotemporal relations (e.g. Recognition of faces, music in-terpretation, voice recognition, recognition of an object by their form) – dur to functionof parieto-occipital cortex b) Lesion of this hemisphere produces inability of recognition (cannot recognizeother people´s feelings) 101 – Role of the cortical motor areas in motor control. Several areas of the cerebral cortex are designated as motor areas. These includethe primary motor cortex (area 4, motor strip, MI), premotor cortex (areas 6 and 8),supplementary motor cortex (portion of area 6), and secondary motor cortex (MII).
127. The primary motor cortex (area 4) is located in the precentral gyrus and therostral half of the paracentral lobule. Direct electrical stimulation of this area evokesmovements associated with the voluntary muscles on the contralateral side. A map ofthis electrically excitable cortex produces a somatotopically organized motorhomunculus. The homunculus hangs upside down with the larynx and tongue in thelowest part adjacent to the lateral fissure, followed upward by the head, upper limb,thorax, abdomen, and lower extremity; the latter is located in the rostral paracentralgyrus. The amount of motor cortex devoted to specific regions is roughly proportionalto the skill, precision, and control of the movements in that region (e.g., large area forlarynx, tongue, thumb, and lips). The role of area 4 is to participate in the execution ofskilled and agile voluntary movements. The premotor cortex, located rostral to area 4, consists of areas 6 and 8. Area 8,known as the frontal eye field, is concerned with eye movements. Stimulation of thisarea results in conjugate movements of the eyes directed to the opposite side. Thepremotor cortex on the lateral surface of the lobe has (1) a primary role in the control ofthe proximal limb and axial musculature and (2) an essential role in the initial phases oforientation movements of the body and upper limbs directed toward a target. The supplementary motor cortex, located on the medial aspect of area 6, has asomatotopic organization. It is important for programming of patterns and sequences ofmovements The descending motor pathways are subdivided into systems called the 1. corticospinal and corticobulbar tracts, 2. corticoreticulospinal pathways, 3. corticorubrospinal pathway, 4. corticotectospinal pathway, 5. vestibulospinal tracts, 6. raphe–spinal and ceruleus– spinal pathways (aminergic pathways). These pathways are involved with motor circuits associated with the spinal cordand spinal nerves. These systems also have equivalent roles influencing local motorcircuits of the brainstem and the cranial nerve47 – Draw and describe simplified scheme of a neuronal chain of pathways for thenociceptive information. Nociceptors are free nerve endings. There are three types of receptors activatedby different noxious stimuli. Mechanical nociceptors are activated by mechanical
128. stimuli (e.g., sharp pricking); thermal and mechano-thermal receptors are activated bystimuli that cause slow, burning pain; and polymodal receptors are activated bymechanical stimuli as well as temperature (e.g., hot, cold, burning sensation) Information regarding fast and acute pain sensations is conducted to the CNS bysmall, myelinated A fibers; conduction velocity in these fibers is much faster than thatof C fibers. Slow, chronic pain sensation is carried to the CNS by unmyelinated Cfibers. Both types of fibers enter the spinal cord at the apex of the dorsal horn, branch,and then ascend and descend for one to three segments and then enter the dorsal horn. The cell bodies of sensory neurons mediating pain are located in the dorsal rootganglia (first-order neurons). The nociceptors represent nerve endings of the peripheralaxons of the sensory neurons located in the dorsal root ganglia. The central axons (bothA and C fibers) of these sensory neurons reach the dorsal horn and branch intoascending and descending collaterals, forming the dorsolateral tract (fasciculus) ofLissauer. In Lissauers tract, these fibers (A and C fibers) ascend or descend a few spinalsegments, enter the gray matter of the dorsal horn, and synapse on neurons located inlaminae I and II (substantia gelatinosa). Sensory information from laminae I and II istransmitted to second-order neurons located in laminae IV to VI. The second-orderneurons in laminae IV to VI are collectively called the principal sensory nucleus(nucleus proprius). The neospinothalamic tract is the major ascending pathway involved inconveying pain signals to the higher centers; it arises from the nucleus proprius(principal sensory nucleus). The axons of the principal sensory nucleus, which mediatenociceptive signals, cross to the contralateral side in the anterior (ventral) whitecommissure of the spinal cord and form the neospinothalamic tract in the lateralfuniculus. The neospinothalamic tract then ascends through the medulla, pons, and themidbrain and projects upon neurons located in the ventral posterolateral nucleus andposterior nuclei of the thalamus. Axons of the thalamic neurons project to the primarysensory cortex. The neospinothalamic tract gives off many collaterals and makesconnections with the brainstem reticular formation.44 – Draw and describe simplified scheme of a neuronal chain of anterolateral sys-tem of the somatosensory pathways, cite corresponding modalities.
129. There are two components of pain: the sensory discriminative component, whichsignals the location, intensity, and quality of the noxious stimululation, and theaffective-motivational component of pain which signals the unpleasant quality of theexperience, and enables the autonomic activation that follows a noxious stimulus. Thediscriminative component is thought to depend on pathways that target the traditionalsomatosensory areas of cortex, while the affective- motivational component is thoughtto depend on additional cortical and brainstem pathways. Pathways responsible for the discriminative component of pain originate withother sensory neurons, in dorsal root ganglia and, like other sensory nerve cells thecentral axons of nociceptive nerve cells enter the spinal cord via the dorsal roots. Whenthese centrally projecting axons reach the dorsal horn of the spinal cord, they branchinto ascending and descending collaterals, forming the dorsolateral tract of Lissauer.Axons in Lissauer’s tract typically run up and down for one or two spinal cord segmentsbefore they penetrate the gray matter of the dorsal horn. Once within the dorsal horn,the axons give off branches that contact neurons located in several of Rexed’s laminae.The axons of these second order neurons in the dorsal horn of the spinal cord cross themidline and ascend all the way to the brainstem and thalamus in the anterolateralquadrant of the contralateral half of the spinal cord. These fibers form the spinothalamictract, the major ascending pathway for information about pain and temperature. Thisoverall pathway is also referred to as the anterolateral system, much as themechanosensory pathway is referred to as the dorsal column–medial lemniscus system. 48 – Describe somatrotopic arrangement of the somatosensory pathwaysand cortex. Dorsal column
130. The discriminative general senses pathway is serially organized as a basicsequence of three orders of neurons conveying information to the cerebral cortex.Information from the body, limbs, and back of the head is conveyed from the peripheralreceptors over first-order neurons of the spinal nerves with cell bodies in the dorsal rootganglia. Their heavily myelinated fibers enter the spinal cord as the medial bundle ofthe dorsal roots and branch into (1) collaterals, which terminate mainly in laminae III and IV of the posterior horn (2) fibers that ascend in the ipsilateral fasciculi gracilis and cuneatus of the dorsal (posterior) column before terminating in the nuclei gracilis and cuneatus of the lower medulla. Some of the collaterals ending in the posterior horn synapse with interneuronsinvolved with spinal reflex arcs. The ascending axons of the dorsal column– mediallemniscus pathway exhibit a somatotopically organized lamination according to bodyarea innervated. Fibers are added to the lateral aspect of the dorsal column (fasciculigracilis and cuneatus) at each successively higher spinal cord level. The medial– laterallamination at upper cervical levels consists, in sequence, of fibers from sacral, lumbar,thoracic, and cervical segments of the body. Fibers from the sacral, lumbar, and lowersix thoracic levels compose the fasciculus gracilis of the posterior column and those ofthe upper six thoracic and all cervical levels (includes innervation of the back of head)form the fasciculus cuneatus. The fibers terminating in the nucleus gracilis originatefrom below T6 (including the lower extremity); those terminating in the nucleuscuneatus originate from above T6, including the upper extremities. The proprioceptivefibers from the lower extremity ascend in the dorsolateral fasciculus with the fibers ofthe lateral cervical system to the lateral cervical nucleus. Following neural processingwithin the nucleus gracilis and nucleus cuneatus information is projected to the ventralposterolateral (VPL) nucleus of the thalamus.. There are somatotopic projections (1) from the medial lemniscus and spinothalamictracts to the VPL nucleus and (2) from the core and shell of VPL to somatosensorycortex (areas 1, 2, 3a, and 3b). 66 – Describe a projection of the visual information to the tectum,hypothalamus and their functional significances. Neurons in the suprachiasmatic nucleus of the hypothalamus also appear to playan important role in the sleep-wakefulness cycle. These neurons show a clear-cutdiurnal rhythm for light and darkness. They receive direct retinal inputs , and if the
131. nucleus is destroyed, other rhythms, such as those for endocrine function and sleep-wakefulness cycles, are disrupted. Light that stimulates the retina activates light-detecting retinal ganglion neuronswhose dendrites contain the photopigment melanopsin. These widely dispersed neurons,constituting about 2% of retinal ganglion cells, have tortuous broad overlappingdendritic fields optimally arranged to detect low levels of light. Following stimulation,this population fires continuously without adaptation for at least 20 minutes, in contrastto ganglion cells that receive input from rods and cones. Activation of the melanopsin-containing ganglion cells, which project directly to the suprachiasmatic nucleus via theretinohypothalamic tract, entrains mammalian circadian rhythms to environmental time. The Retino–Superior–Colliculus (Retino-Tectal) Pathways for Coordinating Eye and Head Movements The superior colliculus has a major role in coordinating eye and neckmovements to detect, capture, track, and maintain the visual image on the fovea. Thesuperficial layers of the superior colliculus receive direct visual input from the retinaand indirect input from the visual cortex. Visual information is coordinated withauditory and vestibular inputs, which are distributed to the intermediate layers. Thesuperior colliculus controls the proper tracking of the eyes to a vast number ofenvironmental stimuli. Superior colliculus cells are especially responsive to motionwithin the receptive field. Descending projections from the visual cortex and the frontaleye fields (Brodmann’s area 8) project to the superior colliculus and to the paramedianpontine and midbrain gaze centers for control or horizontal and vertical eye movement(EOM. The gaze centers provides the basis for integrated EOMs in response to sensoryinformation that helps to locate moving objects in space. The deeper layers of thesuperior colliculus project to the gaze centers and are the source of the tectospinal tractfor coordination of head and eye positions and tectopontine fibers for relay to thecerebellum. As with other muscle groups, the coordination of eye muscles is influencedby the cerebellum and basal ganglia 118 – Components of a defensive response.
132. When large portions of the sympathetic nervous system discharge at the sametime-that is a mass discharge-this increases in many ways the ability of the body toperform vigorous muscle activity (fight-or-flight). Effects of the sympathetic system:− Increase arterial pressure− Increase blood flow to active muscles concurrent with a decrease blood flow to organs such as the gastrointestinal tract and the kidneys that are not needed for rapid motor activity.− Increased rates of cellular metabolism throughout the body− increased blood glucose due to increased glicolysis in liver and muscle.− Incresed muscle strenght− increased mental activity− increased role of blood coagulation. The sum of these effects permits to perform much more stenuous physysicalactivity than would otherwise be possible. Because it is mental as physical stress that virtually excites the sympatheticsystem, it is frequently said that the purpose of the sympathetic system, is to provideextra activation of the body in states of stress-sympathetic stress purpose. 99 – Control of posture. The vestibular nuclei are the major destination of the axons that form thevestibular division of the eighth cranial nerve; as such, they receive sensory informationfrom the semicircular canals and the otolith organs that specifies the position andangular acceleration of the head. Many of the cells in the vestibular nuclei that receive
133. this information are upper motor neurons with descending axons that terminate in themedial region of the spinal cord gray matter, although some extend more laterally tocontact the neurons that control the proximal muscles of the limbs. The projections fromthe vestibular nuclei that control axial muscles and those that influence proximal limbmuscles originate from different cells and take different routes (called the medial andlateral vestibulospinal tracts). Other upper motor neurons in the vestibular nuclei projectto lower motor neurons in the cranial nerve nuclei that control eye movements (thethird, fourth, and sixth cranial nerve nuclei). This pathway produces the eye movementsthat maintain fixation while the head is moving. The reticular formation is acomplicated network of circuits located in the core of the brainstem that extends fromthe rostral midbrain to the caudal medulla and is similar in structure and function to theintermediate gray matter in the spinal cord. Unlike the well defined sensory and motornuclei of the cranial nerves, the reticular formation comprises clusters of neuronsscattered among a welter of interdigitating axon bundles; it is therefore difficult tosubdivide anatomically. The neurons within the reticular formation have a variety offunctions, including cardiovascular and respiratory control, governance of myriadsensory motor reflexes, the organization of eye movements, regulation of sleep andwakefulness, and, most important for present purposes, the temporal and spatialcoordination of movements. The descending motor control pathways from the reticularformation to the spinal cord are similar to those of the vestibular nuclei; they terminateprimarily in the medial parts of the gray matter where they influence the local circuitneurons that coordinate axial and proximal limb muscles. Both the vestibular nuclei and the reticular formation provide information to thespinal cord that maintains posture in response to environmental (or selfinduced)disturbances of body position and stability. As expected, the vestibular nuclei makeadjustments in posture and equilibrium in response to information from the inner ear.Direct projections from the vestibular nuclei to the spinal cord ensure a rapidcompensatory response to any postural instability detected by the inner ear. In contrast,the motor centers in the reticular formation are controlled largely by other motor centersin the cortex or brainstem. The relevant neurons in the reticular formation initiateadjustments that stabilize posture during ongoing movements. The way the upper motorneurons of the reticular formation maintain posture can be appreciated by analyzingtheir activity during voluntary movements. Even the simplest movements areaccompanied by the activation of muscles that at first glance seem to have little to dowith the primary purpose of the movement.98 – Reflexes in motor control. Reflex responses are mediated by neuronal linkages called reflex arcs or loops.The structure of a spinal somatic reflex arc can be summarized in the following manner.
134. (1) A sensory receptor responds to an environmental stimulus. (2) An afferent fiber conveys signals through the peripheral nerves to the gray matter of the spinal cord. (3a) In the simplest reflex arc, the afferent root enters the spinal cord and synapses directly with lower motoneurons (monosynaptic). (3b) In more complex, and more common, reflex arcs, the afferent root synapses with interneurons, which, in turn, synapse with lower motoneurons (polysynaptic reflex). (4) A lower motoneuron transmits impulses to effectors—striated voluntary (skeletal) muscles. Spinal reflexes are also classified as 1. segmental, 2. intersegmental, 3. suprasegmental A segmental reflex comprises neurons associated with one or even a few spinalsegments. An intersegmental reflex consists of neurons associated with several to manyspinal segments. A suprasegmental reflex involves neurons in the brain that influencethe reflex activity in the spinal cord. Reflexes in which the sensory receptor is in themuscle spindle of any muscle group are known as myotatic, stretch, or deep tendonreflexes (DTR). These are intrasegmental reflexes. Examples are: (1) the biceps reflex— tapping the biceps brachii tendon results in flexion of the forearm at the elbow, (2) the triceps reflex—tapping the triceps tendon results in extension of the forearm at the elbow, (3) the quadriceps reflex (knee jerk—tapping of the quadriceps tendon results in extension of the leg at the knee, and (4) the triceps sural reflex (ankle jerk)—tapping of the Achilles tendon results in plantar flexion of the foot.77 – Draw and describe simplified scheme of a neuronal chain of the vestibularpathways.
135. The purpose of the vestibular system is to signal changes in the motion of thehead (kinetic) and in the position of the head with respect to gravity (static). Theinformation from the periphery required by the nervous system to perform these roles isobtained from three afferent sources: the eyes, general proprioceptive receptorsthroughout the body, and the vestibular receptors in the inner ear. These three afferentsources are integrated into three systems (visual, proprioceptive and vestibular systems)known as the equilibrial triad. The vestibular system is a special proprioceptive systemthat functions to maintain equilibrium, to direct the gaze of the eyes, and to preserve aconstant plane of vision (head position), primarily by modifying muscle tone. Input to the Vestibular Nuclei The sensory neurons of the vestibular nerve (cell bodies in the vestibularganglion) are bipolar with distal branches that terminate on the hair cells of thevestibular receptors (maculae and cristae ampullares). Most of the centrally directedaxons terminate ipsilaterally within the brainstem in precise synaptic patterns withineach of the four vestibular nuclei (superior, lateral, medial, and inferior). In general, thefibers originating from the cristae ampullares end in the medial and superior nuclei; thefibers originating in the maculae of the utricle and saccule terminate primarily in thelateral, inferior, and medial vestibular nuclei. Other fibers of the vestibular nerve coursethrough the juxtarestiform body and end directly in the ipsilateral cerebellar cortex,chiefly in the flocculonodular lobe, which is referred to as the vestibulocerebellum. Inaddition, this cortex and the fastigial nuclei of the cerebellum send crossed anduncrossed fibers to the vestibular nuclei. In summary, the vestibular nuclei receive theirmain input both from the vestibular receptors and the cerebellum. In addition, thevestibular nuclei have reciprocal connections with the flocculonodular lobe and nucleifastigii of the cerebellum.Output From the Vestibular Nuclei The influences from the vestibular nuclei are projected 1. to the spinal cord via the (lateral) vestibulospinal tract and medial vestibulospinal tract (within medial longitudinal fasciculus [MLF]), 2. to the cerebellum via fibers in the juxtarestiform body 3. to the brainstem primarily via the MLF (vestibulomesencephalic fibers)