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Sammelmappe1

  1. 1. BIOLOGICAL PSYCHOLOGY I Giorgia Silani giorgia.silani@sissa.it
  2. 2. STRUCTURE OF THE COURSE: WHEN• Thursday 21/10/2010: 12 -17• Friday 22/10/2010: 10-15• Thursday 11/11/2010: 12 -17• Friday 12/11/2010: 10-15• Thursday 02/12/2010: 12 -17• Friday 03/12/2010: 10-15
  3. 3. STRUCTURE OF THE COURSE: HOW• 50 minutes: Frontal Lecture…but open to discussion. •Feel free to ask questions!• 10 minutes BREAK: you and me to recover a bit!• After each topic, some practical exercise…good training for the finalexam
  4. 4. STRUCTURE OF THE COURSE: WHAT• Chapter 01: Historical review .• Chapter 02: Cell biology of neurons• Chapter 03 - 04: Physiology of neural membrane• Chapter 05 - 06: Communication between neurons• Chapter 07: Anatomy of the nervous system• Chapter 08: Smell and Taste• Chapter 09 - 10: Visual system• Chapter 11: Auditory system• Chapter 12: Somatic sensory system• Chapter 13 - 14: Motor systemsTextbook: Bear, Connors, Paradiso “Neuroscience,exploring the brain – 3rd edition”Additional material on the webpage of the course Take home message…a lot of stuff to do.
  5. 5. STRUCTURE OF THE COURSE: WHOTorino, Italy Milano, Italy London, UK Trieste, Italy Zurich, Switzerland
  6. 6. LET’S START
  7. 7. NEUROSCIENCE:PAST, PRESENT, AND FUTURE
  8. 8. THE ORIGINS OF NEUROSCIENCENeuroscience is the scientific study of the nervoussystem.Relatively young term (Society for Neuroscience 1969)..but curiosity about the brain and how it works is old asmuch as the mankind itself
  9. 9. 7000 B.C. ... long time ago• Prehistoric ancestors – Brain vital to life• Skull surgeries – Evidence: Trepanation – Skulls show signs of healing
  10. 10. 5000 B.C. ... Ancient EgyptHeart: Seat of soul and memory (not the head)Mummification processCanopic Jars were used to hold the organs of the dead after they wereembalmed.The four organs housed by the jars were the lungs, the stomach, the liverand the intestines.Egyptians held no regard for the brain, which was discarded.The heart (scarab) was left inside the body, to be judged in the afterlife
  11. 11. 500 B.C. ... Ancient GreeceHippocrates (460 -379 B.C.) • Brain: Involved in sensation; • Seat of intelligenceAristotle (384 -322 B.C.) • Heart: centre of intellect; • Brain: Radiator for the cooling of the blood
  12. 12. A.D. ... Roman EmpireGalen (130 -200 A.D.)Correlation between structure and function • Cerebrum: soft = sensations • Cerebellum: hard= movements • Ventricles: contains fluids which movements to or from regulate perception and actions
  13. 13. From Reinassance to the XIX CenturyThe Renaissance Fluid-mechanical theory of brain function Philosophical mind-brain distinction Descartes (1596-1650)The Seventeenth and Eighteenth Centuries Gray matter and white matter observation Basic anatomical subdivisions of PNS and CNS Identifications of gyri, sulci, and fissuresBeginning of the Nineteenth Century Nerve as wires, understanding of electrical phenomena, brain can generate electricity Studies of Charles Bell and Francois Magendie on ventral and dorsal roots of the nerves
  14. 14. the XIX CenturyLocalization of Function in the Brain . If spinal roots carry differential functional information then different parts of the brain are specialized to process this information 1809 - Phrenology Franz Joseph Gall 1823 - Experimental ablation method Marie-Jean-Pierre Flourens 1861 – Lesioned patients Paul Broca
  15. 15. the XIX CenturyCerebral localization in animals Neuron as the basic Nervous systems of different function of the brain species may share common mechanisms
  16. 16. Neuroscience todayLevels of AnalysisMolecular (i.e. neurotransmitter, enzymes etc.)Cellular (i.e. types of neurons and their properties)Systems (i.e. visual, auditory etc.)Behavioral (from networks to behaviors)Cognitive ( from brain to mind, i.e. consciousness)
  17. 17. Neuroscientists
  18. 18. The cost of ignorance
  19. 19. NEURONS AND GLIA
  20. 20. CELLS IN THE NERVOUS SYSTEMGlia Neurons Process informationInsulates, supports, Sense environmental changesand nourishes Communicate changes to other neuronsneurons Command body response
  21. 21. THE NEURON DOCTRINECells are in the range of 0.01 – 0.05 mm of diameterNeed for techniques that allow to see such small structuresHistology Microscopic study of tissue structure The Nissl Stain (late XIX century) Colors selectively only part of the cell (Nissl body) Facilitates the study of cytoarchitecture in the CNS Differentiation between neuron and glia The Golgi Stain (1873) Revealed the entire structure of the neuron
  22. 22. THE NEURON DOCTRINE
  23. 23. THE NEURON DOCTRINECamillo Golgi’s reticular theoryNeurites of different cells are fused together to form a continuous reticulum, anetwork (like blood circulation)Santiago Ramon y Cajal’s neuron doctrineNeuron are not continuous one another but communicate by contact Shared the 1906 Nobel Prize in Physiology or Medicine
  24. 24. THE NEURONNeuronal membraneseparate the inside from the outsideThe SomaCytosol: Watery fluid inside the cellOrganelles: Membrane-enclosedstructures within the soma Nucleus Rough Endoplasmatic Reticulum, Smooth Endoplasmatic Reticulum, Golgi Apparatus MitochondriaCytoplasm: Contents within a cellmembrane (e.g., organelles, excludingthe nucleus)
  25. 25. THE NUCLEUSContains chromosomes that have thegenetic material (DNA)Genes: segment of DNAGene expression: reading of DNA in orderto synthesize proteinsProtein synthesis happen in the cytoplasmRNA is the messenger that carry theinformation contained in the DNA to thecytoplasm
  26. 26. THE NUCLEUSThe enzyme RNA polymerase binds to the promoter of the gene in order to initiatetranscriptionExons: coding regionsIntrons: non –coding regionsIn the cytoplasm mRNA transcriptis used to assemble proteinsfrom amino acidsDNA transcription mRNA translation Proteins
  27. 27. ROUGH ENDOPLASMATIC RETICULUM Major site for protein synthesis Contains ribosomes attached to the ER and free ribosomesCytosol Membrane
  28. 28. SMOOTH ER and GOLGI APPARATUSSites for preparing/sorting proteins for delivery to different cell regions (trafficking)and regulating substances
  29. 29. THE MITOCHONDRIONSite of cellular respiration (inhale andexhale)Pyruvic acid and O2, trough the Krebscycle are transformed in ATP and CO21 Pyruvic acid = 17 ATPATP- cell’s energy source (by breakdownof ATP in ADP)
  30. 30. THE NEURONAL MEMBRANEBarrier that encloses cytoplasm~5 nm thickProtein concentration in membrane variesStructure of discrete membrane regions influences neuronalfunction
  31. 31. THE CYTOSKELETONNot staticInternal scaffolding of neuronal membraneThree “bones” Microtubules Microfilaments NeurofilamentsMicrotubulesBig and run longitudinally along the neuron.MicrofilamentsSame size of the membrane. Role in changing cellshapeNeurofilamentsMediam size. Structurally very strong
  32. 32. THE AXONThe Axon is specialized for the transferinformation over long distances Axon hillock (beginning) Axon proper (middle) Axon terminal (end)Differences between axon and soma ER does not extend into axon (This means no protein synthesis there) Protein composition: Unique Variable diameter and length
  33. 33. THE SYNAPSEThe axon terminal is the site of contact withanother neuron or cell (synapse) andtransfer of information (synaptictransmission)In the Axon Terminal there are nomicrotubulesPresence of synaptic vesicles (containneurotransmitter)Abundance of membrane proteins postsynapsis)Large number of mitochondria
  34. 34. THE AXOPLASMIC TRANSPORTAllows the transport of the proteinssynthesized in the soma to the axonterminalAnterograde (soma to terminal):could be fast (1000mm per day) orslow (1-10 mm per day). Legs areKinesinRetrograde (terminal to soma)transport: feedback information.Legs are dynein
  35. 35. THE DENDRITE“Antennae” of neuronsAll the dendrites of a neuron are called dendritic treeDendritic spinesPostsynaptic: receives signals from axon terminal by using proteinmolecules called receptors that detect neurotransmitters in the synapticcleft
  36. 36. CLASSIFICATION OF NEURONSClassification Based on the Number of Neurites Single neurite Unipolar Two or more neurites Bipolar- two Multipolar- more than twoClassification Based on Dendritic and Somatic Morphologies Stellate cells (star-shaped) and pyramidal cells (pyramid- shaped) Spiny or aspinous
  37. 37. CLASSIFICATION OF NEURONSFurther Classification By connections within the CNS Primary sensory neurons, motor neurons, interneurons Based on axonal length Golgi Type I - long axon, projection neurons Golgi Type II - short axon, local circuit neurons Based on neurotransmitter type e.g., – Cholinergic = Acetycholine at synapses
  38. 38. GLIAMainly supports neuronal functionsAstrocytes Most numerous glia in the brain Fill spaces between neurons (Influence neurite growth) Regulate the chemical context of the external environment of the neurons Myelinating Glia Oligodendroglia (in CNS) and Schwann cells (in PNS) insulate axons Node of Ranvier: region where the axonal membrane is exposed
  39. 39. THE NEURAL MEMBRANE AT REST
  40. 40. ELECTRICAL PROPERTIESSimple reflex : information needs to be quickly transmitted to the CNS and backInformation is transmitted through action potentials (change in the electrical properties of themembrane)Cells able to generate an AP have excitable membraneAt rest, these cells have a inside negative electrical charge (resting membrane potential) thatbecome positive during the AP
  41. 41. CYTOSOLIC AND EXTRACELLULAR FLUIDWater is the key ingredient in intracellular and extracellular fluidKey feature – uneven distribution of electrical charge (O has a net negativecharge)Ions are atoms or molecules with a net electrical charge dissolved in the waterSalz for example is a crystal of Sodium (Na+) and Chloride (Cl-)Monovalent Ion: Difference between protons and electrons =1,Divalent Ion: Difference between protons and electrons =2,cation (+), anion (-)When the crystal breaks down spheres ofhydration -layer of water are attracted to the ionThe orientation of the water molecules isdetermined by the valence of the ion
  42. 42. IONS INVOLVED IN CELLULAR PHYSIOLOGY Sodium Calcium + 2+Potassium Chloride + -
  43. 43. THE PHOSPHOLIPID MEMBRANEHydrophilic: Dissolve in water due to uneven electrical charge (e.g., salt,proteins, carbohydrates)Hydrophobic: Does not dissolve in water due to even electrical charge (e.g., oil,lipids in general) The Phospholipid Bilayer Hydrophilic HydrophobicResting and Action potentials depend on special proteins that are inserted in themembrane
  44. 44. THE PROTEINProteins are molecules assembled by combination of different amino acids (20 types) Central alpha carbon R group Amino group Carboxyl group
  45. 45. THE PROTEIN STRUCTURE Peptide bondPrimary Tertiary Secondary Quaternary
  46. 46. CHANNEL PROTEINSIon ChannelsThey form a pore through the membrane that hydrophilicis ion selectiveThey can be opened and closed (gated)by changing in the local microenvironmentof the membrane hydrophobicIon PumpsFormed by membrane spanning proteinsUses energy from ATP breakdownNeuronal signaling
  47. 47. THE MOVEMENT OF IONSDiffusion: movement of ion due to concentration levelsDissolved ions tend to distribute evenly by following down concentration gradientConcentration gradient = difference of concentration of an ion across the membraneElectricityElectrical current (I, measured in Amperes) represents ion movement.It’s regulated by1) electrical conductance (g, measured in Siemens) or electrical resistance (R, measured in Ω): ability (or inability) of an electrical charge to migrate from one point to another2) electrical potential (V, measured in volts): difference in chargebetween cathode and anode
  48. 48. THE MOVEMENT OF IONSElectrical current flows across the membrane byOhm’s law relationshipI =gV or I =V/R Membrane potential: Voltage across the neuronal membrane. The resting potential is typically -65 mV …let’ see why…
  49. 49. EQUILIBRIUM POTENTIALExample 1 Equilibrium is reached when diffusional and electricalExample 2 forces are equal and opposite (equilibrium potential, Eion)
  50. 50. MEMBRANE POTENTIALIn the membrane ions have different concentration between inside and outside,and this gradient is established by action of ionic pumps, that use energy inorder to move ions against concentration forces Membrane permeability determines membrane resting and action potentials
  51. 51. MEMBRANE POTENTIAL Membrane permeability determines membrane resting and action potentialsMembrane rest potential is determined by the higher number of K vs. Na channelsopen (resting potential close to Ek potential)
  52. 52. THE ACTION POTENTIAL
  53. 53. ACTION POTENTIALConveys information over distance in the nervous systemRapid reversal of the membrane potential at rest
  54. 54. ACTION POTENTIALThe Generation of an Action Potential is caused by depolarization of themembrane beyond threshold“All-or-none” eventChain reactione.g., Puncture foot, stretch membrane of nerve fibersOpens Na+-permeable channels Na+ influx depolarizedMembrane reaches threshold action potential
  55. 55. ACTION POTENTIALA way to study the properties of AP is the Generation of Multiple Action Potentials Artificially - inject current into a neuron using a microelectrode
  56. 56. ACTION POTENTIALFiring frequency reflects the magnitude of the depolarizing currentThe maximum firing frequency is 1000 Hz. This means that after an AP, is notpossible to initiate another one for at least 1 msec (absolute refractory period).Also the initiation of another AP after few msec requires more current(relative refractory period).
  57. 57. THE ACTION POTENTIAL IN THEORYIf only K+ channel are open then the membrane would reach EK+
  58. 58. THE ACTION POTENTIAL IN THEORYBut if the membrane is also permeable to Na+ , the EP will go towards ENa+ Rising phase (depolarization): Inward sodium current Falling phase (repolarization): Outward potassium current
  59. 59. THE ACTION POTENTIAL IN REALITYFirst described by Hodgkin and Huxley, with the use of a voltage Clamp: “Clamp”membrane potential at any chosen value Rising phase  transient increase in gNa, influx of Na+ ions Falling phase  increase in gK, efflux of K+ ions Existence of sodium “gates” in the axonal membrane sensitive to change in membrane potential and selective for Na
  60. 60. THE ACTION POTENTIAL IN REALITYThe Voltage-Gated Sodium Channel 1) sensitivity to change in membrane potential 2) selectivity for Na
  61. 61. THE ACTION POTENTIAL IN REALITYThe Voltage-Gated Sodium Channel Open with little delay Stay open for about 1msec Cannot be open again by depolarization (Absolute refractory period: Channels are inactivated)
  62. 62. THE ACTION POTENTIAL IN REALITYThe Voltage-Gated Potassium Channels Open in response to depolarization but later than sodium gates Potassium conductance serves to rectify or reset membrane potential (Delayed rectifier) Structure: Four separate polypeptide subunits join to form a pore
  63. 63. THE ACTION POTENTIAL IN REALITY To summarize- Key Properties of the Action Potential are •Threshold •Rising phase •Overshoot •Falling phase •Undershoot •Absolute refractory period •Relative refractory period
  64. 64. THE ACTION POTENTIAL CONDUCTIONDown axon to the axon terminal Orthodromic: Action potential travels in one direction Antidromic (experimental): Backward propagationTypical conduction velocity: 10 m/sec and length of action potential: 2 msec
  65. 65. THE ACTION POTENTIAL CONDUCTIONFactors Influencing Conduction Velocity: 1) Spread of action potential along membrane follows the path of less resistance. It depends upon axon structure and direction of positive charge 2) Path of the positive charge Inside of the axon (faster) Across the axonal membrane (slower) 3) Axonal excitability Axonal diameter (bigger = faster) Number of voltage-gated channels opens
  66. 66. THE ACTION POTENTIAL CONDUCTIONLayers of myelin sheath facilitates current flow (saltatory conduction) Myelinating cells 1) Schwann cells in the PNS 2) Oligodendroglia in CNS
  67. 67. THE ACTION POTENTIAL CONDUCTIONSaltatory conduction 0.2 - 2 mm
  68. 68. THE ACTION POTENTIAL INITIATION
  69. 69. SYNAPTIC TRANSMISSION
  70. 70. SYNAPTIC TRANSMISSION 1897: Charles Sherrington- “synapse” The process of information transfer at a synapse Plays role in all the operations of the nervous systemInformation flows in one direction: Neuron to target cell First neuron = Presynaptic neuron Target cell = Postsynaptic neuron Types of synapses: 1) Chemical (1921- Otto Loewi) 2) Electrical (1959- Furshpan and Potter)
  71. 71. ELECTRICAL SYNAPSES Gap junction Cells are said to be “electrically coupled” Flow of ions from cytoplasm to cytoplasm and in both directions Transmission is fast
  72. 72. ELECTRICAL SYNAPSESAn AP in the pre synaptic cell, generate a PSP (post synaptic potential) in thepost synaptic cellIf several PSPs occur simultaneously to excite a neuron this generates an AP(Synaptic integration)
  73. 73. CHEMICAL SYNAPSESKey elements:Synaptic cleft (wider the gap junction);Presynaptic element (usually an axon terminal )Synaptic vesicles (storage of neurotransmitter)Secretory granules (bigger vesicles)Postsynaptic density (receptor that converts chemical signalinto electrical signal )Postsynaptic cell
  74. 74. CNS SYNAPSESAxodendritic: Axon to dendriteAxosomatic: Axon to cell bodyAxoaxonic: Axon to axonDendrodendritic: Dendrite to dendrite Gray’s Type I: Asymmetrical, excitatory Gray’s Type II: Symmetrical, inhibitory
  75. 75. NEUROMUSCULAR JUNCTIONSynaptic junction outside the CNSStudies of NMJ establishedprinciples of synaptic transmissionOne of the largest and fastersynapses in the body
  76. 76. PRINCIPLES OF CHEMICAL SYNAPTIC TRANSMISSIONBasic Steps • Neurotransmitter synthesis • Load neurotransmitter into synaptic vesicles • Vesicles fuse to presynaptic terminal • Neurotransmitter spills into synaptic cleft • Binds to postsynaptic receptors • Biochemical/Electrical response elicited in postsynaptic cell • Removal of neurotransmitter from synaptic cleft
  77. 77. PRINCIPLES OF CHEMICAL SYNAPTIC TRANSMISSIONNeurotransmittersAmino acids: Small organic moleculesstored in and released from synapticvesicles (Glutamate, Glycine, GABA)Amines: Small organic molecules storedin and released from synaptic vesicles(Dopamine, Acetylcholine, Histamine)Peptides: Short amino acid chains (i.e.proteins) stored in and released fromsecretory granules (Dynorphin,Enkephalins)
  78. 78. PRINCIPLES OF CHEMICAL SYNAPTIC TRANSMISSIONNeurotransmitter Synthesis and StorageA part from amino acids, amines and peptides are synthesized from precursors only in neuronthat release them.Amine and amino acids are synthesized in the axon terminal and the take up by the vesicleswith the help of the transportes .Peptides are synthesized in the rough ER, eventually split in the Golgi apparatus and thencarried to the axon terminal in the secretory granules
  79. 79. PRINCIPLES OF CHEMICAL SYNAPTIC TRANSMISSIONNeurotransmitter release by exocytosisAP opens voltage gate calcium channelProcess of exocytosis stimulated by release of intracellular calcium, [Ca2+]I, due to the AP.Vesicle membrane fuses into presynaptic membrane with subsequent release of neurotransmitterVesicle membrane recovered by endocytosis and then refilled with new neurotransmitter
  80. 80. PRINCIPLES OF CHEMICAL SYNAPTIC TRANSMISSIONNeurotransmitter Receptors and Effectors (postsynaptic cell)Ionotropic: Transmitter-gated ion channels Metabotropic: G-protein-coupled receptor Autoreceptors: Presynaptic receptors sensitive to neurotransmitter released by presynaptic terminal. Act as safety valve to reduce release when levels are high in synaptic cleft (autoregulation)
  81. 81. PRINCIPLES OF CHEMICAL SYNAPTIC TRANSMISSION EPSP: Transient postsynaptic membrane depolarization by presynaptic release of neurotransmitterIPSP: Transient hyperpolarizationof postsynaptic membranepotential caused by presynapticrelease of neurotransmitter
  82. 82. PRINCIPLES OF CHEMICAL SYNAPTIC TRANSMISSIONNeurotransmitter Recovery and DegradationNeurotransmitter must be cleared from the synaptic cleft. Different ways.Diffusion: Away from the synapseReuptake: Neurotransmitter re-enters presynaptic axon terminalEnzymatic destruction inside terminal cytosol or synaptic cleftDesensitization: e.g., AChE cleaves Ach to inactive state
  83. 83. PRINCIPLES OF SYNAPTIC INTEGRATIONSynaptic IntegrationProcess by which multiple synaptic potentials combine within one postsynapticneuron
  84. 84. PRINCIPLES OF SYNAPTIC INTEGRATIONQuantal Analysis of EPSPsThe synaptic vesicle is the elementary units of synaptic transmissionThe amplitude of an EPSP is some multiple of the response to the content of a vesicle(quantum)Quantal analysis is used to determine number of vesicles that release duringneurotransmissionMiniature postsynaptic potential (“mini”) are normally generated spontaneously
  85. 85. PRINCIPLES OF SYNAPTIC INTEGRATIONEPSP SummationAllows for neurons to perform sophisticated computations. EPSPs are added together toproduce significant postsynaptic depolarization. Two types:Spatial: EPSP generated simultaneously in different spacesTemporal: EPSP generated at same synapse in rapid succession
  86. 86. PRINCIPLES OF SYNAPTIC INTEGRATION Inhibition Action of synapses to take membrane potential away from action potential thresholdIPSPs and Shunting InhibitionExcitatory vs. inhibitory synapses: Binddifferent neurotransmitters (GABA or Glycine),allow different ions to pass through channels(Chloride, Cl-)Membrane potential less negative than -65mV= hyperpolarizing IPSPShunting Inhibition: Inhibiting current flow fromsoma to axon hillock
  87. 87. PRINCIPLES OF SYNAPTIC INTEGRATIONThe Geometry of Excitatory and Inhibitory SynapsesExcitatory synapses (Glutamate) usually have Gray’s type I morphologyClustered on soma and near axon hillockInhibitory synapses (GABA, Glycine) have Gray’s type II morphology Gray’s Type I: Asymmetrical, excitatory Gray’s Type II: Symmetrical, inhibitory
  88. 88. PRINCIPLES OF SYNAPTIC INTEGRATIONModulationSynaptic transmission that modifies effectiveness of EPSPs generated by othersynapses with transmitter-gated ion channels Example: Activating NE β receptor
  89. 89. NEUROTRANSMITTER SYSTEMS
  90. 90. NEUROTRANSMITTERBasic criteria:1. The molecule must be synthetized and stored in the presynaptic neuron2. The molecule must be released by the presynaptic axon terminal uponstimulation3. The molecule, when experimentally applied, must produce a response in thepostsynaptic cell that mimics the response generated by the release of theneurotransmitter by the presynaptic cell
  91. 91. HOW TO STUDY NEUROTRASMITTERSLocalization of Transmitters and Transmitter-synthesizing enzyme Immunocytochemistry Anatomically localize particular molecules to particular cells
  92. 92. HOW TO STUDY NEUROTRASMITTERSStudying Transmitter Localization In situ hybridization mRNA strands can be detected by complementary probe Probe can be radioactively labeled - autoradiography
  93. 93. HOW TO STUDY NEUROTRASMITTERSStudying Transmitter Release Loewi and Dale identified Ach as a transmitter CNS contains a diverse mixture of synapses that use different neurotransmitters impossible to stimulate a single population of synapses Brain slice as a model (ex vivo, brain in a dish) Kept alive in vitro  Stimulate synapses, collect and measure released chemicals (mixture) Often stimulated by high K+ solution to cause massive synaptic release Ca2+ dependency of the release has to be confirmed
  94. 94. HOW TO STUDY NEUROTRASMITTERSStudying Receptors No two transmitters bind to the same receptor; however one neurotransmitter can bind to many different receptors Receptor subtypes Neuropharmacology Subtype specific agonists and antagonists ACh receptors Skeletal muscle Heart
  95. 95. HOW TO STUDY NEUROTRASMITTERSStudying Receptors
  96. 96. HOW TO STUDY NEUROTRASMITTERSStudying ReceptorsLigand-binding methods Drugs that interact selectively with neurotransmitter receptors were used to analyze natural receptors Solomon Snyder and opiates Identified receptors in brain Subsequently found endogenous opiates Endorphins, dynorphins, enkephalins Enormously important for mapping the anatomical distribution of different neurotransmitter receptors in brain
  97. 97. NEUROTRASMITTER CHEMISTRYCholinergic (ACh) Neurons good marker for cholinergic neurons Rate-limiting step of Ach synthesis Secreted from the axon terminal and associated with axon terminal membrane
  98. 98. NEUROTRASMITTER CHEMISTRYCholinergic (ACh) Neurons Synthesis Degradation
  99. 99. NEUROTRASMITTER CHEMISTRYCatecholaminergic Neurons Involved in movement, mood, attention, and visceral function Tyrosine: Precursor for three amine neurotransmitters that contain catechol group Dopamine (DA) Norepinephrine (NE, noradrenaline) Epinephrine (E, adrenaline)
  100. 100. NEUROTRASMITTER CHEMISTRY Marker for catecholaminergic neurons Rate limiting, regulated by physiological signals •Low-rate release - increased catecholamine conc. - inhibit TH activity •High-rate release - increased Ca2+ influx - boost TH activity Present in the synaptic vesicles Present in the cytosolReleased from the adrenal gland as well
  101. 101. NEUROTRASMITTER CHEMISTRY• Serotonergic Neurons – Serotonin (5-HT,5- hydroxytryptamine) is derived from tryptophan – Regulates mood, emotional behavior, sleep – Synthesis of serotonin • Limited by the availability of blood tryptophan (diet) – Selective serotonin reuptake inhibitors (SSRIs): Antidepressants
  102. 102. NEUROTRASMITTER CHEMISTRY• Amino Acidergic Neurons – Amino acid neurotransmitters: Glutamate, glycine, gamma- aminobutyric acid (GABA) – Glutamate and glycine • Present in all cells - Differences among neurons are quantitative NOT qualitative • Vesicular transporters are specific to these neurons – Glutamic acid decarboxylase (GAD) • Key enzyme in GABA synthesis • Good marker for GABAergic neurons • One chemical step difference between major excitatory transmitter and major inhibitory transmitter
  103. 103. THE CENTRAL NERVOUS SYSTEM
  104. 104. ANATOMICAL REFERENCES AXIAL Caudal/ Rostral/Lateral Medial Posterior Anterior Dorsal CORONAL Ventral Rostral/ Anterior SAGITTAL Caudal/ Medial PosteriorLateral
  105. 105. THE MENINGES space membrane space Artery BrainThe meninges are filled with cerebrospinal fluid (CSF) Insula
  106. 106. Whole Brain GM WM CSF
  107. 107. THE CNSCerebrum Brainstem Cerebellum
  108. 108. MAJOR SULCI Longitudinal sulcus
  109. 109. MAJOR SULCI Central sulcusLateral (sylvian) fissure
  110. 110. CEREBRAL LOBES ParietalFrontal Occipital Temporal
  111. 111. CEREBRAL LOBES Insula
  112. 112. CEREBELLUMLeft Cerebellar Hemisphere Right Cerebellar Hemisphere Insula Vermis
  113. 113. WHITE MATTER TRACTSLeft Cerebellar Hemisphere Right Cerebellar Hemisphere Insula Vermis
  114. 114. FUNCTIONAL CLASSIFICATION
  115. 115. BROADMANN’S CLASSIFICATION Insula
  116. 116. THE CNS Thalamus Telencephalon Pineal bodyDiencephalon Hypothalamus Tegment Tectum Cerebellum Midbrain Pons Medulla Insula
  117. 117. THE VENTRICULAR SYSTEMLateralventricles Third ventricle Fourth ventriclethird Fourth ventricleventricle Fourth ventricle fourth ventricle Lateral ventricles Fourth ventricle Insula
  118. 118. THALAMIC NUCLEI Insula
  119. 119. CEREBRAL CIRCULATION Anterior Cerebral Artery Anterior Communicating Artery Middle Cerebral Artery Internal Carotid ArteryPosteriorCommunicating Artery Posterior Cerebral Artery Superior Cerebellar Artery Basilar Artery Insula Vertebral Arteries
  120. 120. CEREBRAL CIRCULATION Terminal branches of Anterior Cerebral ArteryMiddle Cerebral Artery Terminal branches of Posterior Cerebral Artery Insula
  121. 121. CEREBRAL CIRCULATIONAnterior CerebralArtery Posterior Cerebral Artery Insula Posterior Communicating Artery
  122. 122. CEREBRAL CIRCULATION Anterior Cerebral Artery Surface branches supply cortex and white matter of : 1)inferior frontal lobe 2)medial surface of the frontal and parietal lobes 3)anterior corpus callosum Posterior Cerebral Artery Surface branches supply cortex and white matter of: 1)medial occipital lobes 2)inferior temporal lobes 3)posterior corpus callosum Middle Cerebral Artery Surface branches supply cortex and white matter of: hemispheric convexity (all four lobes and insula). Insula
  123. 123. CEREBRAL CIRCULATIONMiddle Cerebral Artery StrokeMost common stroke syndrome. Symptoms:-contralateral weakness (face, arm, and hand more than legs)-contralateral sensory loss (face, arm, and hand more than legs)-visual field cut (damage to optic radiations)-aphasia: language disturbances (more likely with L. Hemi. Damage)-impaired spatial perception (more likely after R. Hemi. Damage) Insula
  124. 124. CEREBRAL CIRCULATION Anterior Cerebral Artery - Motor disturbance contralateral distal leg - urinary incontinence - speech disturbance (may be more of a motor problem) - apraxia of left arm (sympathetic apraxia) if anterior corpus callosum is affected - if bilateral may cause apathy, motor inertia, and mutenessPosterior Cerebral ArteryVisual disturbances:-contralateral homonymous hemianopsia (central vision is often spared)-L. Hemi: lesions alexia (with or without agraphia)-Bilateral lesions: cortical blindness : patients unaware they cannot see-Memory impairment if temporal lobe is affected Insula
  125. 125. CRANIAL NERVES Insula Posterior Communicating Artery
  126. 126. THE CHEMICAL SENSES
  127. 127. THE CHEMICAL SENSESAnimals depend on the chemical senses to identify nourishmentChemical sensation Oldest and most common sensory system with the aim to detect environmental chemicalsChemical senses Gustation & Olfaction (separate but processed in parallel) Chemoreceptors
  128. 128. TASTEThe Basics Tastes Saltiness, sourness, sweetness, bitterness, and umami. Innate preferences and rejections for particular tastes (sweet and bitter) have a survival reasons Usually there is correspondence between chemical ingredients and taste: Sweet—sugars like fructose, sucrose, artificial sweeteners (saccharin and aspartame) Bitter—ions like K+ and Mg2+, quinine, and caffeine Salty—salts Sour—acids How to distinguish the countless unique flavors of a food 1) Each food activates a different combination of taste receptors 2) Distinctive smell (it combines with taste to give the flavor) 3) Other sensory modalities (texture and temperature)
  129. 129. TASTEThe Organs of Taste Tongue, mouth, palate, pharynx, and epiglottis Nasal cavity for smell
  130. 130. TASTEAreas of sensitivity on the tongue (but most of the tongue is sensitive to all basicstastes) Tip of the tongue: Sweetness Back of the tongue : Bitterness Sides of tongues: Saltiness and sournessPapillae (taste receptors)FoliateVallateFungiformAt threshold concentration(just enough exposure ofsingle papilla to detect taste)they respond to only one taste.More concentrations lead toless selectivity
  131. 131. TASTETastes Receptor Cells Apical end is the chemically sensitive part. It has small extensions called microvilli that project into the taste pore. Receptor potential: Voltage shift – depolarization of the membrane cause CA++ entering the cell and release of transmitter
  132. 132. TASTETransduction: process by an environmental stimulus cause an electrical responsein a sensory receptor.In the case of taste, chemical stimuli (tastants) may:1)Pass directly through ion channels2)Bind to and block ion channels3)Bind to G-protein-coupled receptorsSlightly different mechanisms for saltiness, sourness, bitterness, sweetness andumami (amino acids)
  133. 133. TASTESaltinessSpecial Na+ selective channel.The ion pass directly through channelcausing deporalizationSournessSourness- acidity – low pHH + binds to and block ion channelscausing deporalization
  134. 134. TASTEBitternessBitter substances are detected by different typesT1R and T2R receptor. They work as G-proteincoupled receptorsSweetnessIt also detected by receptors T1R2+T1R thathave the same signaling mechanism (cf. bittertaste)The expressed in different taste cells allow thesystem not to be confused about the tasteUmamiUmami receptors T1R1+T1R3 detect aminoacids
  135. 135. TASTEBitterness Sweetness Umami
  136. 136. TASTE VII Facial nerve IX Glossopharyngeal nerve X Vagus nerve They carry primary gustatory axons Gustatory nucleus Point where taste axons bundle and synapse Ventral posterior medial nucleus (VPM) Deals with sensory information from the head Primary gustatory cortex (Insula) Receives axons from VPM taste neurons Lesion in VPM and Gustatory cortex can cause ageusia- the loss of taste perception
  137. 137. SMELLSmell is not only important for taste but also for social communicationPheromones are important signals • Reproductive behavior • Territorial boundaries • Identification • Aggression
  138. 138. SMELLThe Organs of Smell1)Olfactory epithelium: contains olfactory receptor cells, supporting cells (produce mucus),and basal cells (source of new receptor cells)2)Olfactory axons constitute olfactory nerve3)Cribriform plate: A thin sheet of bone through which small clusters of axons penetrate,coursing to the olfactory bulbAnosmia: Inability to smell
  139. 139. SMELL Olfactory TransductionReceptor potential: if strong enough generates APs in the cell body andspikes will propagate along the axon
  140. 140. SMELLAdaptation: decreased response despite continuous stimulus. Common features of sensoryreceptors across modalities Each receptor cell express a single olfactory receptor protein. They responds to different odours but with preferences. Many different cells are scattered into the epithelium
  141. 141. SMELLCentral Olfactory PathwaysMapping of receptor cell into glomeruli is extremely precise
  142. 142. SMELLAxons of the olfactory tract branch and enter the forebrain (unconscious perception)bypassing the thalamusNeocortex (conscious perception) is reached by a pathway that synapses in the medialdorsal nucleus of the thalamus
  143. 143. THE EYE
  144. 144. LIGHTVision is probably the most important sense in humans and animals. This system works bytransducing the property of light into a complex visual perceptLight is an electromagnetic radiation visible to the eye. It’s defined by 3 parameters:wavelength (distance btw two peaks or troughs)frequency (number of waves per second)amplitude (difference btw wave trough and peak)The energy content of a radiation isproportional to his frequency.Only a small part of theelectromagnetic spectrum is visibleto our eyes
  145. 145. LIGHTOptics is the study of light rays and their interactionsReflection: bouncing of light rays off a surfaceAbsorption: transfer of light energy to a particle or surfaceRefraction: changing of a direction due to change in speed of light rays, due to the passing from onemedium to another
  146. 146. ANATOMY OF THE EYEPupil: Opening where light entersthe eyeSclera: White of the eyeIris: Gives color to eyes. Contains 2muscles that give size to the pupilCornea: Glassy transparent externalsurface of the eyeExtraocular muscles: move theeyeball in the orbitOptic nerve: Bundle of axons fromthe retina
  147. 147. THE RETINAOptic disk: where blood vesselsoriginate and axons leave the retinaMacula: part of retina for centralvisionFovea: marks the center of the retina
  148. 148. CROSS SECTION OF THE EYECiliary muscles: Ligaments that suspend lensLens: Change shape to adjust focus. It divides eyes into two compartments:1) anterior chamber containing aqueous humor2) posterior chamber containing vitreous humor zonule fibers retina iris lens fovea light cornea aqueous humor optic nerve ciliary muscles vitreous humor sclera
  149. 149. IMAGE FORMATIONEye collects light, focuses on retina, forms images.The cornea is the site of most of the refractive power of the eye Focal distance: from refractive surface to the point where the rays converges. Depends on the curvature of the cornea
  150. 150. IMAGE FORMATIONAccommodation by the Lens Changing shape of lens allows for extra focusing power
  151. 151. IMAGE FORMATION
  152. 152. IMAGE FORMATIONThe Pupillary Light Reflex Depends on connections between retina and brain stem neurons that control muscle around pupil and aim to continuously adjust to different ambient light levels. It is consensual for both eyesThe Visual Field Amount of space viewed by the retina when the eye is fixated straight aheadVisual Acuity Ability to distinguish two nearby points Visual Angle: Distances across the retina described in degrees
  153. 153. MICROSCOPIC ANATOMY OF THE RETINAPhotoreceptors: cells that convert light energy into neural activityIn the Retina cells are organized in layers . Inside-out
  154. 154. MICROSCOPIC ANATOMY OF THE RETINAPhotoreceptor Structure Transduction of electromagnetic radiation to neural signals Four main regions 1) Outer segment 2) Inner segment 3) Cell body 4) Synaptic terminal Types of photoreceptors Rods (scotopic vision-dark) and cones (photopic vision-light)
  155. 155. MICROSCOPIC ANATOMY OF THE RETINARegional Differences in Retinal StructureVaries from fovea to retinal periphery In peripheral retina there is higher ratio of rods to cones, and higher ratio of photoreceptors to ganglion cells resulting in more sensitive to light In the fovea (pit in retina) visual acuity is maximal. In Central fovea there are only cones (no rods) and 1:1 ratio with ganglion cells
  156. 156. PHOTOTRANSDUCTIONPhototransduction in Rods Depolarization in the dark: “Dark current” and hyperpolarization in the light One opsin in rods: Rhodopsin Receptor protein that is activated by light G-protein receptor Photopigment
  157. 157. PHOTOTRANSDUCTIONDepolarization in the dark:“Dark current” andhyperpolarization in the light:Constant inward sodiumcurrentLight activate an enzime thatdestroy the cGMP, causingthe closing of Na+ channel
  158. 158. PHOTOTRANSDUCTION
  159. 159. PHOTOTRANSDUCTIONPhototransduction in Cons Similar to rod phototransduction Different opsins sensitive to different wavelengths: Red, green, blueColor detection is determined by the relativecontributions of blue, green, and red cones toretinal signal (Young-Helmholtz trichromacytheory of color vision)Dark and Light Adaptation is the transitionfrom photopic to scotopic vision (20-25minutes). It’s determined by: Dilation of pupils Regeneration of unbleached rhodopsin Adjustment of functional circuitry
  160. 160. RETINAL PROCESSINGPhotoreceptors release glutamate when depolarizedBipolar Cells. Can be categorized in 2 classes: OFF bipolar cells (they respond toglutamate by depolarizing) and ON bipolar cells (they respond to glutamate byhyperpolarizing) . Light off or on causes depolarization
  161. 161. RETINAL PROCESSINGGanglion Cell Receptive Fields On-Center and Off-Center cells Responsive to differences in illumination
  162. 162. RETINAL PROCESSINGTwo types of ganglion cells in monkey and human retina M-type (Magno) and P-type (Parvo) – 5 and 90 % of the ganglion cell population. The rest 5 % is non-P and non-M cells M-type: larger receptive field, faster conduction of AP, more sensitive to low contrast stimuliColor-Opponent Ganglion Cells
  163. 163. RETINAL PROCESSING
  164. 164. THE CENTRAL VISUAL SYSTEM
  165. 165. RETINOFUGAL PROJECTIONIt’s the neural pathway that leaves the eye and it include:The Optic Nerve, Optic Chiasm, and Optic Tract
  166. 166. RETINOFUGAL PROJECTIONThe visual field is the entire region of the space that could be seen by both eye looking straight ahead. Right and Left Visual Hemifields are defined by the space divided by the midline temporal retina nasal temporal retina retina
  167. 167. RETINOFUGAL PROJECTION LGN Optic radiation R optic tractretina V1 R LGN R optic radiation V1
  168. 168. RETINOFUGAL PROJECTION Transection Optic nerve Transection Optic chiasmTransectionOptic tract
  169. 169. THE LATERAL GENICULATE NUCLEUSIn the LGN is present the segregation of input by Eye and by Ganglion Cell Type
  170. 170. THE STRIATE CORTEXRetinotopy Neighboring representation of the object are spatially kept along all the visual pathway In the cortex there is an overrepresentation of central visual field Perception is based on the brain’s interpretation of this information
  171. 171. THE STRIATE CORTEX
  172. 172. THE STRIATE CORTEXLamination of the Striate Cortex (I – VI) Spiny stellate cells: Spine-covered dendrites mainly in layer IVC, they receive information from LGN Pyramidal cells: Spines; thick apical dendrite; mainly layers III, IVB, V, VI Inhibitory neurons: Lack spines; All cortical layers; Forms local connections Magnocellular LGN neurons: Project to layer IVCα Parvocellular LGN neurons: Project to layer IVCβ Koniocellular LGN axons: Bypasses layer IV to make synapses in layers II and III
  173. 173. THE STRIATE CORTEXOutputs of the Striate Cortex: Layers II, III, and IVB: Projects to other cortical areas Layer V: Projects to the superior colliculus and pons Layer VI: Projects back to the LGN Receptive Fields in Layer IV C Layer IVC: Monocular; center-surround receptive field (like in LGN) Layer IVCα: Insensitive to the wavelength – projection from Magno Layer IVCβ: Center-surround color opponency - projection from Parvo Binocularity Layers superficial to IVC: First binocular receptive fields in the visual pathway
  174. 174. THE STRIATE CORTEXOcular Dominance ColumnsInformation coming from the left and the right eye (already segregate in LGN) is keptseparate in layer IV of the visual cortex Only on layer III mixing of the information from the two eyes
  175. 175. THE STRIATE CORTEXCytochrome Oxidase Blobs Cytochrome oxidase is a mitochondrial enzyme used for cell metabolism Blobs: Cytochrome oxidase staining in cross sections of the striate cortex. Each centered on a ocular dominance stripe in layer IV Color-sensitive, monocular, with no orientation or direction selectivity. They are specialized for the analysis of object color The neuron observed in the space between Blobs (interblob) are binocular, with orientation or direction selectivity.
  176. 176. THE STRIATE CORTEXReceptive Fields outside Layer IVC Orientation Selectivity: Neuron fires action potentials in response to bar of particular orientation
  177. 177. THE STRIATE CORTEXReceptive Fields Direction Selectivity: Neuron fires action potentials in response to moving bar of light
  178. 178. THE STRIATE CORTEXParallel Pathways: Magnocellular; Koniocellular; Parvocellular
  179. 179. THE STRIATE CORTEXCortical Module: dimension of 2x2mm.Necessary and sufficient module for the visual perception
  180. 180. THE EXTRASTRIATE CORTEXDorsal stream (V1, V2, V3, MT, MST, Otherdorsal areas) Analysis of visual motion and the visual control of action In Area MT (temporal lobe) most cells: Direction-selective; Respond more to the motion of objects than their shape Area MST (parietal lobe) for navigation, directing eye movements, motion perceptionVentral stream (V1, V2, V3, V4, IT, Otherventral areas) Perception of the visual world and the recognition of objects, Area V4 orientation and perception of color Area IT is major output of V4. Receptive fields respond to a wide variety of colors and abstract shapes. Important also for memory
  181. 181. THE AUDITORY AND VESTIBULAR SYSTEMS
  182. 182. THE NATURE OF SOUNDSound is an audible variations in air pressure, defined by:1) frequency: Number of cycles (distance between successive compressed patches)per second expressed in units called Hertz (Hz). Human Range is btw 20 Hz to 20,000 Hz2) Intensity: Difference in pressure between compressed and rarefied patches of air. Itdetermines the loudness of the sound.Sounds propagate at a constant speed: 343 m/sec
  183. 183. THE AUDITORY SYSTEM
  184. 184. THE MIDDLE EARSound Force (pressure) is amplified by the Ossicles, producing greater pressure at oval window(smaller surface) than tympanic membrane, in order to move more efficiently the fluid inside thecochelaThe Attenuation Reflex: response where onset of loud sound causes tensor tympani andstapedius muscle contraction. It’s used to adapt ear to loud sounds, or understand speech betterin noisy environment (more attenuation of low sounds)
  185. 185. THE INNER EARPerilymph: Fluid in scala vestibuli and scala tympaniEndolymph: Fluid in scala mediaEndolymph has an electric potential 80 mV more positive than perilymph (Endocochlear potential)
  186. 186. THE INNER EARBasilar Membrane is wider at apex, stiffness decreases from base to apex
  187. 187. THE INNER EARPressure at oval window, pushes perilymph into scala vestibuli, round window membrane bulgesout. Endolymph movement bends basilar membrane near base, wave moves towards apex
  188. 188. THE INNER EARThe Organ of Corti and Associated Structures. Here the mechanical energy of thesound is transformed in electrical signal by the auditory receptor cells (hair cells).Each hair cells has around 100 stereocilia.Rods of corti provide structural support. Hair cells form synapses with bipolar neuronsthat have their body in the spiral ganglion. Their axons form the auditory nerve
  189. 189. THE INNER EARTransduction by Hair CellsWhen sound arrives, basilar membrane moves. According to the movement, stereociliabends on one or the other direction: i.e. Basilar membrane upward, reticular lamina upand stereocilia bends outward
  190. 190. THE AUDITORY PATHWAY Auditory cortex A1MGN MGN Superior olive Auditory nerve
  191. 191. INFORMATION ABOUT THE SOUNDInformation About Sound Intensity is encoded in 2 ways: Firing rates of neurons and number of active neuronsStimulus Frequency Frequency sensitivity: in Basilar membrane is Highest at base, lowest at cochlea apex. This coding is kept separate along the auditory pathways (tonotopy)Phase Locking is another way to code for frequency Consistent firing of cell at same sound wave phase. Only for frequency below 4kHz
  192. 192. SOUND LOCALIZATION: HORIZONTAL PLANEInteraural time delay: Time taken for Interaural intensity difference: Sound atsound to reach from ear to ear high frequency from one side of ear Sound Sound Sound shadow waves waves Sound waves Sound waves Sound shadow Sound shadow Duplex theory of sound localization: Interaural time delay: 20-2000 Hz Interaural intensity difference: 2000-20000 Hz
  193. 193. SOUND LOCALIZATION: VERTICAL PLANE pinna Path 2, direct sound Path 2, reflected sound Path 2, direct sound Path 2, reflected sound Path 3, direct sound Path 3, reflected soundBased on reflections from the pinna
  194. 194. THE AUDITORY CORTEX: BA 41Axons leaving MGN project to auditory cortex viainternal capsule in an array called AcousticRadiation Primary auditory cortex Secondary auditory cortex
  195. 195. THE VESTIBULAR SYSTEM Importance of Vestibular System Balance, equilibrium, posture, head position, eye movementThe Vestibular Labyrinth
  196. 196. THE VESTIBULAR SYSTEMThe Otolith Organs (saccule and utricle). Detect force of gravity (linear acceleration)and tilts (change of angle) of the head.Saccule is vertically oriented and utricle horizontally oriented Crystals of calcium carbonate Bending of the hairs toward kinocilium: depolarization
  197. 197. THE VESTIBULAR SYSTEMThe Semicircular Canals. Detect rotation of the head and angular acceleration Crista: Sheet of cells where hair cells of semicircular canals clustered Ampulla: Bulge along canal, contains crista Cilia: Project into gelatinous cupula Kinocili oriented in same direction so all excited or inhibited together Filled with endolymph Three semicircular canals on one side helps sense all possible head- rotation angles Each Canal paired with another on opposite side of head Rotation causes excitation on one side, inhibition on the other endolymph
  198. 198. CENTRAL VESTIBULAR PATHWAY S1/M1 Face area
  199. 199. VESTIBULO-OCULAR REFLEX (VOR) Motion of the headFunction: Line of sight fixed on Motion of the eyesvisual targetMechanism: Senses rotations ofhead, commands compensatorymovement of eyes in oppositedirection.Connections from semicircularcanals, to vestibular nucleus, tocranial nerve nuclei exciteextraocular muscles
  200. 200. THE SOMATO-SENSORY SYSTEM
  201. 201. SOMATIC SENSATION Enables body to feel, ache, chill. Responsible for feeling of touch and pain Different from other systems because receptors are widely distributed throughout all the body and responds to different kinds of stimuliTypes and layers of skin Hairy and glabrous (hairless) Epidermis (outer) and dermis (inner)Functions of skin Protective function Prevents evaporation of body fluids Provides direct contact with worldMechanoreceptors Most somatosensory receptors are mechanoreceptors. Pacinian corpuscles Ruffinis endings Meissners corpuscles Merkels disks Krause end bulbs
  202. 202. TOUCH RECEPTORS
  203. 203. TOUCH RECEPTORSTwo-point discrimination varies across the body surface (Importance of fingertips overelbow). Difference in density of receptors, size of receptive fields, brain tissue devolved inprocessing the information Big toe sole calf back lip forearm thumb Index finger
  204. 204. PRIMARY AFFERENT AXONS white matter Gray matter Dorsal root Big toe Dorsal root ganglion Dorsal root ganglion cell receptor Dorsal Spinal root nerve lip Primary Afferent Axons Aα, Aβ, Aδ, C C fibers mediate pain and temperature A β mediates touch sensations
  205. 205. PRIMARY AFFERENT AXONS
  206. 206. THE SPINAL CORDDivided in spinal segments (30)- spinal nerves within 4 divisionsDermatomes (area of the skin innervate by the R and L dorsal roots of a singlespinal segment) have 1-to-1 correspondence with segments
  207. 207. THE SPINAL CORDDivision of spinal gray matter: Dorsal horn; Intermediate zone; Ventralhorn Myelinated Aβ axons (touch-sensitive) mainly synapses in the dorsal horn with the second order sensory neurons
  208. 208. ASCENDING PATHWAYS Dorsal Column–Medial Lemniscal Pathway The Trigeminal Touch Pathway Touch information ascends through dorsal Trigeminal nerves column, dorsal nuclei, medial lemniscus, Cranial nerves and ventral posterior nucleus to primary somatosensory cortex S1 S1 dorsal column nuclei VPN trigeminal nucleus VPNdorsal column Medial lemniscus From face
  209. 209. SOMATOSENSORY CORTEXPrimary is area 3b Receives dense input from VP nucleus of the thalamus Lesions impair somatic sensations Electrical stimulation evokes sensory experiencesArea 3a receive information fromvestibular systemArea 1 receive information from 3b andcode for textureArea 2 receive information from 3b andcode for size and shapeOther areas Posterior Parietal Cortex (5,7)
  210. 210. SOMATOSENSORY CORTEXCortical Somatotopy (Homunculus)
  211. 211. SOMATOSENSORY CORTEXCortical Map PlasticityRemove digits or overstimulate – examinesomatotopy before and afterShowed reorganization of cortical maps
  212. 212. SOMATOSENSORY CORTEXThe Posterior Parietal Cortex Involved in somatic sensation, visual stimuli, and movement planning Lesion has been associated to: Agnosia, Astereoagnosia and Neglect syndrome
  213. 213. PAINPain - feeling associated to nociceptionNociception - sensory process, provides signals that trigger painNociceptors: Transduction of PainBradykinin , Mast cell activation: Release of histamineTypes of Nociceptors: Polymodal, Mechanical, Thermal and ChemicalHyperalgesia: highersensitivity to pain in tissuealready damagedPrimary occurs in thedamaged tissues andsecondary hyperalgesia inthe surroundingsBradykinin, prostaglandins,and substance P(secondary hyperalgesia)
  214. 214. PAINPrimary Afferents First pain mediated by fast axons and second pain by slower C fibers Spinal mechanisms brain Dorsal root Ventral root
  215. 215. PAIN ASCENDING PATHWAYSMain differences between touch and pain pathway Nerve endings in the skin Spinothalamic Pain Pathway Diameter of axons Connections in spinal cord Touch – Ascends Ipsilaterally Pain – Ascends Contralaterally Two pathways: 1) Spinothalamic Pain Pathway 2) The Trigeminal Pain Pathway
  216. 216. PAIN ASCENDING PATHWAYS
  217. 217. REGULATION OF PAINAfferent Regulation: gate theory of pain Dorsal horn To dorsal column To spinothalamic tract
  218. 218. REGULATION OF PAINDescending pain control pathway. Use of serotoninStimulation of the PAG cause deep analgesia The endogenuos opiates Opioids and endomorphins Primary auditory cortex Secondary auditory cortex
  219. 219. TEMPERATUREThermoreceptors “Hot” and “cold” receptors. Varying sensitivitiesThe Temperature Pathway Identical to pain pathway Cold receptors coupled to Aδ and C Hot receptors coupled to C
  220. 220. THE MOTOR SYSTEM, part I
  221. 221. SOMATIC MOTOR SYSTEMMuscles and neurons that control musclesRole: Generation of coordinated movementsParts of motor control Spinal cord coordinated muscle contraction Brain motor programs in spinal cord
  222. 222. SOMATIC MOTOR SYSTEMTypes of MusclesSmooth: digestive tract, arteries, related structuresStriated: Cardiac (heart) and skeletal (bulk of body muscle mass)In each muscle there are 100 of muscle fibers innervated by a single axon from the CNS muscle fibers Axon from CNS muscle
  223. 223. SOMATIC MOTOR SYSTEMSomatic MusculatureAxial muscles: Trunk movementProximal muscles: Shoulder, elbow, pelvis, knee movementDistal muscles: Hands, feet, digits (fingers and toes) movement Antagonist Synergist Flexors Extensors
  224. 224. THE SPINAL CORDThe Lower Motor NeuronLower motor neuron: Innervated by ventralhorn of spinal cordUpper motor neuron: Supplies input to thespinal cord Ventral root Lower motor Ventral horn Spinal neuron nerve Muscle fiber li
  225. 225. THE SPINAL CORDAlpha Motor NeuronsTwo lower motor neurons: Alpha and GammaAlpha Motor Neurons directly trigger the contractionof the muscleMotor Unit: muscle fibers + 1 alpha motor neuronMotor neuron pool: all alpha motor neuron thatinnervate a single muscleGraded Control of Muscle Contraction byAlpha Motor NeuronsVarying firing rate of motor neurons (temporalsummation)Recruit additional synergistic motor units.More motor units in a muscle allow for finelycontrolled movement by the CNS
  226. 226. THE SPINAL CORDInputs to Alpha Motor Neurons1) Information about muscle lenght2) Voluntary control of movement3) Excitatory or inhibitory in order to generate a spinal motor program 3 1 2
  227. 227. THE MOTOR UNITSTypes of Motor UnitsRed muscle fibers: Large number of mitochondria and enzymes, slow to contract, can sustain contractionWhite muscle fibers: Few mitochondria, anaerobic metabolism, contract and fatigue rapidlyFast motor units: Rapidly fatiguing white fibersSlow motor units: Slowly fatiguing red fibersHypertrophy: Exaggerated growth of muscle fibersAtrophy: Degeneration of muscle fibers Normal Crossed innervation innervation slow fast slow fast slow fast Fast like Slow like
  228. 228. THE MOTOR UNITSMuscle fiber structure Mitochondria MyofibrilsSarcolemma: external membraneMyofibrils: cylinders that contract after an APSarcoplasmic reticulum: reach of Ca2+T tubules: network that allow the AP to gothrough T tubules Sarcoplasmic reticulum Opening of T tubules Sarcolemma
  229. 229. THE MOTOR UNITSThe Molecular Basis of Muscle ContractionZ lines: Division of myofibril into segments by disksSarcomere: Two Z lines and myofibrilThin filaments: Series of bristles. Contains actinThick filaments: Between and among thin filaments. ContainsmyosinSliding-filament model: Binding of Ca2+ to troponin causesmyosin to bind to actin. Myosin heads pivot, cause filamentsto slide
  230. 230. THE MOTOR UNITSMuscle contraction Excitation: Action potential, ACh release, EPSP,Alpha motor neurons release ACh action potential in muscle fiber, depolarizationACh produces large EPSP in muscle fibers (via Contraction: Ca2+, myosin binds actin, myosinnicotinic ACh receptors) pivots and disengages, cycle continues untilEPSP evokes action potential. Ca2+ and ATP presentAction potential triggers Ca2+ release, leads to Relaxation: EPSP end, resting potential, Ca2+ byfiber contraction ATP driven pump, myosin binding actin coveredRelaxation, Ca2+ levels lowered by organellereuptake
  231. 231. SPINAL CONTROLMuscle spindles: specialized structures inside the skeletal muscle. They informabout the sensory state of the muscle (proprioception)
  232. 232. SPINAL CONTROLThe Myotatic ReflexStretch reflex: Muscle pulled tendency to pull backFeedback loop. MonosynapticDischarge rate of sensory axons: Related to muscle lengthExample: knee-jerk reflex (stretching the quadriceps and consequent contraction)
  233. 233. SPINAL CONTROLIntrafusal fibers: gamma motor neuronExtrafusal fibers: alpha motor neuron Gamma Loop Provides additional control of alpha motor neurons and muscle contraction Circuit: Gamma motor neuron intrafusal muscle fiber Ia afferent axon alpha
  234. 234. SPINAL CONTROLProprioception from Golgi Tendon Organ.In series with the muscle fibers. Information about the tension applied to the muscleReverse myotatic reflex function: Regulate muscle tension within optimal rangeGolgiTendonOrgan
  235. 235. SPINAL CONTROLSpinal InterneuronsSynaptic inputs1)Primary sensory axons2)Descending axons from brain3)Collaterals of lower motor neuron axonsSynaptic outputs: alpha motor neuronReciprocal inhibition: Contraction of one muscle set Crossed-extensor reflex: Activation of extensoraccompanied by relaxation of antagonist muscle muscles and inhibition of flexors on opposite sideExample: Myotatic reflex flex flex extend extend
  236. 236. MOTOR PROGRAM
  237. 237. THE MOTOR SYSTEM, part II
  238. 238. THE MOTOR SYSTEMThe brain influences activity of the spinal cord in order to generate voluntarymovementsHierarchy of controls Highest level: Strategy, the goal of the movement and best way to achieve it. Associated to neocortex and basal ganglia Middle level: Tactics, the sequence of muscle contraction to achieve the goal. Associate to motor cortex and cerebellum Lowest level: Execution, activation of motor neurons that generate the movement. Associated to brain stem and spinal cord
  239. 239. DESCENDING SPINAL TRACTSAxons from brain descend along two major pathways Lateral Pathways: involved in voluntary of distal musculature movement under cortical control Ventromedial Pathways: involved in control of posture and locomotion, under brain stem control
  240. 240. THE LATERAL PATHWAYS Base of midbrai cerebral n peducle Right red nucleus Medullary pyramid pyramidal decussationCorticospinal Rubrospinaltract tract
  241. 241. THE VENTROMEDIAL PATHWAYSVestibulospinal tract:information from vestibularsystem. Control neck andback muscles. Guide headmovements Vestibular nucleus Vestibulospinal Tectospinal tract tract Spinal cord Tectospinal tract: information from retina and visual system. Guide control eye movements.
  242. 242. THE VENTROMEDIAL PATHWAYSPontine reticulospinal tract:enhance antigravity reflexs,helps maintaining a standingposture Cerebellum pons Pontine reticular formation Medullary reticular formation Reticulospinal tract Medullary reticulospinal tract: opposite function Spinal cord
  243. 243. THE MOTOR CORTEXArea 4 = “Primary motor cortex” or “M1”Area 6 = “Higher motor area”Lateral region Premotor area (PMA), controls distal motor unitsMedial region Supplementary motor area (SMA), controls proximal motor units
  244. 244. THE MOTOR CORTEXThe Contributions of Posterior Parietal and Prefrontal CortexRepresent highest levels of motor control. Help in deciding about actions and their outcome, by integratingmany source of information APs of PMAArea 5: Inputs from areas 3, 1, and 2 neuronArea 7: Inputs from higher-order visual cortical areas.They both project to Area 6 Instruction Trigger
  245. 245. THE BASAL GANGLIABasal ganglia Project to the ventral lateral (VLo) nucleus Provides major input to area 6Cortex Projects back to basal ganglia Forms a “loop” in order to select and initiatiate willed movements
  246. 246. THE BASAL GANGLIAAnatomy of the Basal GangliaCaudate nucleus, putamen, globus pallidus, subthalamic nucleusSubstantia nigra: Connected to basal ganglia
  247. 247. THE BASAL GANGLIAThe Motor Loop: Selection and initiation of willed movementsExcitatory connection from the cortex to cells in putamenCortical activation excites putamen neurons. Inhibits globus pallidus neurons.Release cells in VLo from inhibition. Activity in VLo influences activity in SMA
  248. 248. THE BASAL GANGLIABasal Ganglia Disorders: Hypokinesia and hyperkinesiaParkinson’s diseaseSymptoms: Bradykinesia, akinesia, rigidity and tremors of hand and jawOrganic basis: Degeneration of substantia nigra inputs to striatumDopa treatment: Facilitates production of dopamine to increase SMA activityHuntington’s diseaseSymptoms: Hyperkinesia, dyskinesia, dementia, impaired cognitive disability,personality disorderHemiballismusViolent, flinging movement on one side of the bodySome examples….http://www.youtube.com/watch?v=ECkPVTZlfP8&feature=related PARKINSON
  249. 249. THE CEREBELLUMFunction: Sequence of muscle contractionsLesion: Ataxia, characterized by uncoordinated and inaccurate movements.Dysynergia, dysmetricAnatomy: Folia and lobules, Deep cerebellar nuclei (relay cerebellar cortical outputto brain stem structures) Vermis (contributes to ventromedial pathways) Cerebellarhemispheres (contributes to lateral pathways)
  250. 250. THE CEREBELLUM
  251. 251. THE CEREBELLUMThe Motor Loop Through the Lateral CerebellumAxons from layer V pyramidal cells in the sensorimotor cortex form massive projections to ponsCorticopontocerebellar projection are 20 times larger than pyramidal tractFunction: Execution of planned, voluntary, multijoint movements

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