Central Nervous System 1

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Central Nervous System 1

  1. 1. NERVOUS SYSTEM
  2. 2. NERVOUS FUNCTIONS <ul><li>Body’s master controlling and communicating system </li></ul><ul><li>Three functions </li></ul><ul><ul><li>Sensory input </li></ul></ul><ul><ul><ul><li>Gathers information from sensory receptors </li></ul></ul></ul><ul><ul><li>Integration </li></ul></ul><ul><ul><ul><li>Processes and interprets sensory input </li></ul></ul></ul><ul><ul><li>Motor output </li></ul></ul><ul><ul><ul><li>Activates effector organs to cause a response </li></ul></ul></ul>
  3. 3. Nervous System Organization
  4. 4. ORGANIZATION <ul><li>Two Principal Parts of the System </li></ul><ul><li>Central nervous system (CNS) </li></ul><ul><ul><li>Brain and spinal cord </li></ul></ul><ul><ul><li>Integrating and command center </li></ul></ul><ul><ul><ul><li>Interprets sensory input </li></ul></ul></ul><ul><ul><ul><li>Dictates motor responses </li></ul></ul></ul><ul><li>Peripheral nervous system (PNS) </li></ul><ul><ul><li>Nerves extending from brain and spinal cord </li></ul></ul><ul><ul><li>Carry impulses to and from the CNS </li></ul></ul>
  5. 5. PERIPHERAL DIVISIONS <ul><li>Two Functional Subdivisions of the PNS </li></ul><ul><li>Sensory division </li></ul><ul><ul><li>“ afferent division” </li></ul></ul><ul><ul><li>Nerve fibers conveying impulses to the CNS </li></ul></ul><ul><ul><ul><li>Somatic afferent fibers convey impulses from the skin, muscles, and joints </li></ul></ul></ul><ul><ul><ul><li>Visceral afferent fibers convey impulses from visceral organs </li></ul></ul></ul><ul><li>Motor division </li></ul><ul><ul><li>, “efferent division” </li></ul></ul><ul><ul><li>Nerve fibers conveying impulses from the CNS </li></ul></ul>
  6. 6. ORGANIZATION
  7. 7. HISTOLOGY <ul><li>Nervous system consists mainly of nervous tissue </li></ul><ul><li>Highly cellular </li></ul><ul><ul><li>e.g., <20% extracellular space in CNS </li></ul></ul><ul><li>Two principal cell types </li></ul><ul><ul><li>Neurons </li></ul></ul><ul><ul><ul><li>Excitable nerve cells that transmit electrical signals </li></ul></ul></ul><ul><ul><li>Supporting cells </li></ul></ul><ul><ul><ul><li>Smaller cells surrounding and wrapping neurons </li></ul></ul></ul><ul><ul><ul><li>“ Neuroglia” </li></ul></ul></ul>
  8. 8. NEUROGLIA <ul><li>“ Nerve glue” </li></ul><ul><li>Six types of small cells associated with neurons </li></ul><ul><ul><li>4 in CNS </li></ul></ul><ul><ul><li>2 in PNS </li></ul></ul><ul><li>Most have central cell body and branching processes </li></ul><ul><li>Several functions </li></ul><ul><ul><li>e.g., Supportive scaffolding for neurons </li></ul></ul><ul><ul><li>e.g., Electrical isolation of neurons </li></ul></ul><ul><ul><li>e.g., Neuron health and growth </li></ul></ul>
  9. 9. CNS NEUROGLIA <ul><li>Astrocytes </li></ul><ul><li>Microglia </li></ul><ul><li>Ependymal cells </li></ul><ul><li>Oligodendrocytes </li></ul>
  10. 10. CNS NEUROGLIA <ul><li>Astrocytes </li></ul><ul><li>Most abundant and versatile glial cells </li></ul><ul><li>Numerous processes support branching neurons </li></ul><ul><ul><li>Anchor neurons to capillary blood supply </li></ul></ul><ul><li>Guide migration of young neurons </li></ul><ul><li>Facilitate nutrient delivery to neurons </li></ul><ul><ul><li>(blood  glial cell  neuron) </li></ul></ul><ul><li>Control chemical environment around neurons </li></ul><ul><ul><li>Uptake of K + , neurotransmitters </li></ul></ul><ul><li>Communicate with astrocytes & neurons </li></ul><ul><ul><li>Gap junctions </li></ul></ul>
  11. 11. CNS NEUROGLIA <ul><li>Microglia </li></ul><ul><li>Small ovoid cells </li></ul><ul><li>Relatively long “thorny” processes </li></ul><ul><ul><li>Processes touch nearby neurons </li></ul></ul><ul><li>Migrate toward injured neurons </li></ul><ul><li>Transform into macrophage </li></ul><ul><ul><li>Phagocytize microorganisms, debris </li></ul></ul><ul><ul><li>(Cells of immune system cannot enter the CNS) </li></ul></ul>
  12. 12. CNS NEUROGLIA <ul><li>Ependymal Cells </li></ul><ul><li>Line central cavities of brain and spinal cord </li></ul><ul><ul><li>Form permeable barrier between cerebrospinal fluid inside these cavities and tissue fluid of CNS tissue </li></ul></ul><ul><li>Shapes range from squamous to columnar </li></ul><ul><li>Many are ciliated </li></ul><ul><ul><li>Beating helps circulate cerebrospinal fluid cushioning brain and spinal cord </li></ul></ul>
  13. 13. CNS NEUROGLIA <ul><li>Oligodendrocytes </li></ul><ul><li>Fewer processes than astrocytes </li></ul><ul><li>Wrap processes tightly around thicker neuron fibers in CNS </li></ul><ul><ul><li>“ Myelin sheath” </li></ul></ul><ul><ul><li>Insulating covering </li></ul></ul>
  14. 14. PNS NEUROGLIA <ul><li>Satellite cells </li></ul><ul><li>Schwann cells </li></ul>
  15. 15. PNS NEUROGLIA <ul><li>Satellite cells </li></ul><ul><li>Surround neuron cell bodies within ganglia </li></ul><ul><ul><li>(A ganglion is a collection of nerve cell bodies outside of the CNS) </li></ul></ul><ul><li>Function poorly understood </li></ul>
  16. 16. PNS NEUROGLIA <ul><li>Schwann cells </li></ul><ul><li>“ Neurolemmocytes” </li></ul><ul><li>Surround and form myelin sheaths around larger nerve fibers of PNS </li></ul><ul><ul><li>Functionally similar to oligodendrocytes </li></ul></ul><ul><li>Vital to regeneration of peripheral nerve fibers </li></ul>
  17. 17. NEURONS <ul><li>Nerve cells </li></ul><ul><li>Structural units of nervous system </li></ul><ul><ul><li>Billions are present in nervous system </li></ul></ul><ul><li>Conduct messages throughout body </li></ul><ul><ul><li>Nerve impulses </li></ul></ul><ul><li>Extreme longevity </li></ul><ul><ul><li>Can function optimally for entire lifetime </li></ul></ul><ul><li>Amitotic </li></ul><ul><ul><li>Ability to divide is lost in mature cells </li></ul></ul><ul><ul><li>Cannot be replaced if destroyed </li></ul></ul><ul><ul><ul><li>Some (very few) exceptions </li></ul></ul></ul><ul><ul><ul><li>e.g., stem cells present in olfactory epithelium can produce new neurons </li></ul></ul></ul><ul><ul><li>Stem cell research shows great promise in repairing damaged neurons </li></ul></ul><ul><li>High metabolic rate </li></ul><ul><ul><li>Require large amounts of oxygen and glucose </li></ul></ul>
  18. 18. Neurotrophins <ul><li>Promote neuron growth. </li></ul><ul><li>Nerve growth factors include: </li></ul><ul><ul><li>Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), neurotrophin-3, and neurotrophin-4/5. </li></ul></ul><ul><li>Fetus: </li></ul><ul><ul><li>Embryonic development of sensory neurons and sympathetic ganglia (NGF and neurotrophin-3). </li></ul></ul><ul><li>Adult: </li></ul><ul><ul><li>Maintenance of sympathetic ganglia (NGF). </li></ul></ul><ul><ul><li>Mature sensory neurons need for regeneration. </li></ul></ul><ul><ul><li>Required to maintain spinal neurons (GDNF). </li></ul></ul><ul><ul><li>Sustain neurons that use dopamine (GDNF). </li></ul></ul><ul><li>Myelin-associated inhibitory proteins: </li></ul><ul><ul><li>Inhibit axon regeneration. </li></ul></ul>
  19. 19. Neurons Axon of another neuron Dendrites of another neuron Cell Body Dendrites Axon Myelin Sheath
  20. 20. NEURONS <ul><li>Generally large, complex cells </li></ul><ul><li>Structures vary, but all neurons have the same basic structure </li></ul><ul><ul><li>Cell body </li></ul></ul><ul><ul><li>Slender processes extending from cell body </li></ul></ul><ul><ul><li>Plasma membrane is site of signaling </li></ul></ul>
  21. 21. NEURON CELL BODY <ul><li>Most neuron cell bodies are located in the CNS </li></ul><ul><ul><li>Protected by bones of skull or vertebral column </li></ul></ul><ul><li>Clusters of cell bodies in the CNS are termed “nuclei” </li></ul><ul><li>Clusters of cell bodies in the PNS are termed “ganglia” </li></ul>
  22. 22. NEURON CELL BODY <ul><li>a.k.a., “perikaryon” or “soma” </li></ul><ul><li>5 – 140  m in diameter </li></ul><ul><li>Transparent spherical nucleus </li></ul><ul><ul><li>Contains conspicuous nucleolus </li></ul></ul>
  23. 23. NEURON CELL BODY <ul><li>Major biosynthetic center of neuron </li></ul><ul><li>Other usual organelles present </li></ul><ul><ul><li>ER & ribosomes most active and best developed in body </li></ul></ul><ul><ul><ul><li>What do they do? </li></ul></ul></ul><ul><ul><li>Centrioles absent </li></ul></ul><ul><ul><ul><li>What do centrioles do? </li></ul></ul></ul><ul><ul><li>Sometimes contains pigment inclusions </li></ul></ul>
  24. 24. NEURON CELL BODY <ul><li>Focal point for the outgrowth of neuron processes during embryonic development </li></ul><ul><ul><li>Some processes receive signals </li></ul></ul><ul><ul><li>Plasma membrane generally also acts as part of the receptive surface </li></ul></ul>
  25. 25. NEURON PROCESSES <ul><li>Extend from the neuron’s cell body </li></ul><ul><li>CNS contains both neuron cell bodies and their processes </li></ul><ul><ul><li>Bundles of CNS processes are termed “tracts” </li></ul></ul><ul><li>PNS consists mainly of neuronal processes </li></ul><ul><ul><li>Bundles of PNS processes are termed “nerves” </li></ul></ul><ul><li>Two types of neuron processes </li></ul><ul><ul><li>Dendrites </li></ul></ul><ul><ul><li>Axons </li></ul></ul>
  26. 26. NEURON PROCESSES <ul><li>Typical Dendrite </li></ul><ul><li>Short, tapering, diffusely branching extensions </li></ul><ul><ul><li>Generally hundreds clustering close to cell body </li></ul></ul><ul><ul><li>Most cell body organelles also present in dendrites </li></ul></ul><ul><li>Main receptive / input regions </li></ul><ul><ul><li>Large surface area for receiving signals from other neurons </li></ul></ul><ul><ul><li>Convey incoming messages toward cell body </li></ul></ul><ul><ul><li>Short-distance signals are “graded potentials” </li></ul></ul><ul><ul><ul><li>Not action potentials </li></ul></ul></ul>
  27. 27. NEURON PROCESSES <ul><li>Typical Axon </li></ul><ul><li>Single axon per neuron </li></ul><ul><li>“ Axon hillock” of cell body narrows to form a slender process of uniform diameter </li></ul><ul><li>Sometimes very short </li></ul><ul><li>Sometimes very long </li></ul><ul><ul><li>e.g., axons controlling big toe are 3 – 4 feet long </li></ul></ul>
  28. 28. NEURON PROCESSES <ul><li>Typical Axon </li></ul><ul><li>Single axon may branch along length </li></ul><ul><li>“ Axon collaterals” extend from neurons at ~ 90 o angles </li></ul><ul><li>Usually branches profusely at end </li></ul><ul><ul><li>10,000 or more terminal branches is common </li></ul></ul><ul><ul><li>Distal endings termed “axonal terminals” </li></ul></ul>
  29. 29. NEURON PROCESSES <ul><li>Typical Axon </li></ul><ul><li>Conducting component of neuron </li></ul><ul><li>Generates nerve impulses </li></ul><ul><ul><li>Generated at axon hillock / axon junction in motor neurons </li></ul></ul><ul><ul><li>“ Trigger zone” </li></ul></ul><ul><li>Transmits nerve impulses away from cell body </li></ul><ul><ul><li>To axonal terminals </li></ul></ul>
  30. 30. NEURON PROCESSES <ul><li>Typical Axon </li></ul><ul><li>Axonal terminals are secretory component of neuron </li></ul><ul><li>Sequence of events </li></ul><ul><ul><li>Signal reaches terminals </li></ul></ul><ul><ul><li>Membranes of vesicles fuse with plasma membrane </li></ul></ul><ul><ul><ul><li>“ Axolemma” </li></ul></ul></ul><ul><ul><li>Neurotransmitters released </li></ul></ul><ul><ul><li>Neurotransmitters interact with either other neurons or effector cells </li></ul></ul><ul><ul><ul><li>Excite or inhibit </li></ul></ul></ul>
  31. 31. NEURON PROCESSES <ul><li>Typical Axon </li></ul><ul><li>Contains most of the same organelles found in dendrites and cell body </li></ul><ul><ul><li>Lacks ER and Golgi apparatus </li></ul></ul>
  32. 32. NEURON PROCESSES <ul><li>Typical Axon </li></ul><ul><li>Rely on cell body for some molecules </li></ul><ul><li>Rely on efficient transport mechanisms for delivery </li></ul><ul><ul><li>Anterograde movement toward axonal terminals </li></ul></ul><ul><ul><ul><li>e.g., Mitochondria, membrane components, neurotransmitters or enzymes required for neurotransmitter synthesis, etc. </li></ul></ul></ul><ul><ul><li>Retrograde movement toward cell body </li></ul></ul><ul><ul><ul><li>e.g., Organelles being returned for recycling </li></ul></ul></ul>
  33. 33. NEURON PROCESSES <ul><li>Typical Axon </li></ul><ul><li>Some viruses and bacterial toxins use retrograde transport to reach the cell body </li></ul><ul><ul><li>e.g., poliovirus, rabies virus, herpes simplex viruses, tetanus toxin, etc. </li></ul></ul><ul><li>Such viruses can be used as vehicles for the therapeutic delivery of engineered DNA </li></ul><ul><ul><li>“ Gene therapy” </li></ul></ul>
  34. 34. MYELIN SHEATH <ul><li>Whitish, fatty covering of many nerve fibers </li></ul><ul><ul><li>Particularly those long are large in diameter </li></ul></ul><ul><li>Protects and electrically insulates fibers </li></ul><ul><li>Increases speed of nerve impulse transmission </li></ul><ul><ul><li>Some axons and all dendrites are unmyelinated </li></ul></ul>
  35. 35. MYELIN SHEATH <ul><li>In PNS, myelin sheaths formed by Schwann cells </li></ul><ul><ul><li>Continually wrap around nerve </li></ul></ul><ul><ul><li>Cytoplasm gradually squeezed from intracellular space </li></ul></ul><ul><ul><li>Result is many concentric layers of plasma membrane surrounding the axon </li></ul></ul><ul><ul><ul><li>These plasma membranes contain little protein </li></ul></ul></ul><ul><ul><ul><ul><li>Some proteins present interlock adjacent membranes </li></ul></ul></ul></ul><ul><ul><li>Thickness depends on number of wrappings </li></ul></ul><ul><li>Nucleus and most of cytoplasm exist as a bulge external to the myelin sheath </li></ul><ul><ul><li>“ Neurilemma” </li></ul></ul>
  36. 36. MYELIN SHEATH <ul><li>Adjacent Schwann cells on axon do not touch each other </li></ul><ul><ul><li>Gaps in sheath occur at regular intervals </li></ul></ul><ul><ul><ul><li>“ Nodes of Ranvier” </li></ul></ul></ul><ul><ul><ul><li>a.k.a., “Neurofibril nodes” </li></ul></ul></ul><ul><ul><li>Axon collaterals can emerge at these nodes </li></ul></ul>
  37. 37. MYELIN SHEATH <ul><li>CNS contains both myelinated and unmyelinated axons </li></ul><ul><ul><li>Those long are large in diameter are typically myelinated </li></ul></ul><ul><li>Oligodendrocytes, not Schwann cells, form CNS myelin sheaths </li></ul><ul><ul><li>Oligodendrocytes possess numerous processes that can coil around numerous (up to 60) axons at once </li></ul></ul><ul><ul><ul><li>CNS myelin sheaths lack a neurilemma </li></ul></ul></ul>
  38. 38. MYELIN SHEATH <ul><li>White matter </li></ul><ul><ul><li>Regions of the brain and spinal cord containing dense collections of myelinated fibers </li></ul></ul><ul><li>Gray matter </li></ul><ul><ul><li>Regions of the brain and spinal cord containing mostly nerve cell bodies and unmyelinated fibers </li></ul></ul>
  39. 39. NEURON CLASSIFICATION <ul><li>Structural classification based upon number of processes </li></ul><ul><ul><li>Multipolar neurons </li></ul></ul><ul><ul><li>Bipolar neurons </li></ul></ul><ul><ul><li>Unipolar neurons </li></ul></ul><ul><li>Functional classification based upon direction nerve impulse travels </li></ul><ul><ul><li>Sensory (afferent) neurons </li></ul></ul><ul><ul><li>Motor (efferent) neurons </li></ul></ul><ul><ul><li>Interneurons (association neurons) </li></ul></ul>
  40. 40. NEURON CLASSIFICATION <ul><li>Structural Classification </li></ul><ul><li>Multipolar neurons </li></ul><ul><ul><li>Three or more processes </li></ul></ul><ul><ul><li>Most common neuron type in humans </li></ul></ul><ul><ul><ul><li>(> 99% of neurons) </li></ul></ul></ul><ul><li>Bipolar neurons </li></ul><ul><ul><li>Two processes – axon and dendrite </li></ul></ul><ul><ul><li>Found only in some special sense organs </li></ul></ul><ul><ul><ul><li>e.g., retina of eye </li></ul></ul></ul><ul><ul><li>Act as receptor cells </li></ul></ul><ul><li>Unipolar neurons </li></ul><ul><ul><li>Single short process </li></ul></ul><ul><ul><li>“ Pseudounipolar neurons” </li></ul></ul><ul><ul><ul><li>Originate as bipolar neurons </li></ul></ul></ul><ul><ul><ul><li>Two processes converge and fuse </li></ul></ul></ul><ul><ul><li>Process divides into proximal and distal branches </li></ul></ul><ul><ul><ul><li>Distal process often associated with a sensory receptor </li></ul></ul></ul><ul><ul><ul><ul><li>“ Peripheral process” </li></ul></ul></ul></ul><ul><ul><ul><li>Central process enters CNS </li></ul></ul></ul><ul><ul><li>Most are sensory neurons in PNS </li></ul></ul>
  41. 41. Classification of neurons by shape
  42. 42. NEURON CLASSIFICATION <ul><li>Functional Classification </li></ul><ul><li>Sensory (afferent) neurons </li></ul><ul><ul><li>Transmit impulses toward CNS </li></ul></ul><ul><ul><ul><li>From sensory receptors or internal organs </li></ul></ul></ul><ul><ul><li>Most are unipolar </li></ul></ul><ul><ul><li>Cell bodies are located outside CNS </li></ul></ul><ul><li>Motor (efferent) neurons </li></ul><ul><ul><li>Carry impulses away from CNS </li></ul></ul><ul><ul><ul><li>Toward effector organs </li></ul></ul></ul><ul><ul><li>Multipolar </li></ul></ul><ul><ul><li>Cell bodies generally located in the CNS </li></ul></ul><ul><li>Interneurons </li></ul><ul><ul><li>a.k.a., association neurons </li></ul></ul><ul><ul><li>Lie between motor and sensory neurons in neural pathways </li></ul></ul><ul><ul><li>Shuttle signals through CNS pathways where integration occurs </li></ul></ul><ul><ul><li>> 99% of neurons in body </li></ul></ul><ul><ul><li>Most are multipolar </li></ul></ul><ul><ul><li>Most are confined within the CNS </li></ul></ul>
  43. 43. NEUROPHYSIOLOGY <ul><li>Neurons are highly irritable </li></ul><ul><ul><li>Responsive to stimuli </li></ul></ul><ul><li>Response to stimulus is action potential </li></ul><ul><ul><li>Electrical impulse carried along length of axon </li></ul></ul><ul><ul><li>Always the same regardless of stimulus </li></ul></ul><ul><ul><li>The underlying functional feature of the nervous system </li></ul></ul>
  44. 44. ION CHANNELS <ul><li>Plasma membranes contain various ion channels </li></ul><ul><li>Passive channels (leakage channels) </li></ul><ul><ul><li>Always open </li></ul></ul><ul><li>Active channels (gated channels) </li></ul><ul><ul><li>Ligand-gated channels </li></ul></ul><ul><ul><ul><li>Open when specific chemical binds </li></ul></ul></ul><ul><ul><li>Voltage-gated channels </li></ul></ul><ul><ul><ul><li>Open and close in response to membrane potential </li></ul></ul></ul><ul><ul><li>Mechanically-gated channels </li></ul></ul><ul><ul><ul><li>Open in response to physical deformation of receptor </li></ul></ul></ul><ul><ul><ul><ul><li>e.g., touch and pressure receptors </li></ul></ul></ul></ul>
  45. 45. MEMBRANE POTENTIALS <ul><li>A voltage exists across the plasma membrane </li></ul><ul><ul><li>Due to separation of oppositely charged ions </li></ul></ul><ul><li>Potential difference in a resting membrane is termed its “resting membrane potential” </li></ul><ul><ul><li>~ -70 mV in a resting neuron </li></ul></ul><ul><ul><li>Membrane is “polarized” </li></ul></ul>
  46. 46. MEMBRANE POTENTIALS <ul><li>Neurons use changes in membrane potentials as signals </li></ul><ul><ul><li>Used to receive, integrate, and send signals </li></ul></ul><ul><li>Changes in membrane potentials produced by </li></ul><ul><ul><li>Anything changing membrane permeability to ions </li></ul></ul><ul><ul><li>Anything altering ion concentrations </li></ul></ul><ul><li>Two types of signals </li></ul><ul><ul><li>Graded potentials </li></ul></ul><ul><ul><ul><li>Short-distance signals </li></ul></ul></ul><ul><ul><li>Action potentials </li></ul></ul><ul><ul><ul><li>Long-distance signals </li></ul></ul></ul>
  47. 47. MEMBRANE POTENTIALS <ul><li>Graded Potentials </li></ul><ul><li>Short-lived local changes in membrane potential </li></ul><ul><ul><li>Either depolarizations or hyperpolarizations </li></ul></ul><ul><li>Cause current flows that decrease in magnitude with distance </li></ul><ul><li>Magnitude of potential dependent upon stimulus strength </li></ul><ul><ul><li>Stronger stimulus  larger voltage change </li></ul></ul><ul><ul><li>Larger voltage change  farther current flows </li></ul></ul>
  48. 48. MEMBRANE POTENTIALS <ul><li>Graded Potentials </li></ul><ul><li>Triggered by change in neuron’s environment </li></ul><ul><ul><li>Change causes gated ion channels to open </li></ul></ul><ul><li>Small area of neuron’s plasma membrane becomes depolarized (by this stimulus) </li></ul><ul><li>Current flows on both sides of the membrane </li></ul><ul><ul><li>+ moves toward – and vise versa </li></ul></ul>
  49. 49. MEMBRANE POTENTIALS <ul><li>Graded Potentials </li></ul><ul><li>Inside cell: + ions move away from depolarized area </li></ul><ul><li>Outside cell: + ions move toward depolarized area </li></ul><ul><ul><li>(+ and – ions switch places) </li></ul></ul><ul><li>Membrane is leaky </li></ul><ul><ul><li>Most of the charge is quickly lost through membrane </li></ul></ul><ul><ul><li>Current dies out after traveling a short distance </li></ul></ul>
  50. 50. MEMBRANE POTENTIALS <ul><li>Graded Potentials </li></ul><ul><li>Act as signals over very short distances </li></ul><ul><li>Important in initiating action potentials </li></ul>
  51. 51. MEMBRANE POTENTIALS <ul><li>Action Potentials </li></ul><ul><li>Principal means by which neurons communicate </li></ul><ul><ul><li>Brief reversal of membrane potential </li></ul></ul><ul><ul><ul><li>Total amplitude of ~ 100 mV (-70  +30) </li></ul></ul></ul><ul><ul><li>Depolarization followed by repolarization, then brief period of hyperpolarization </li></ul></ul><ul><ul><li>Time for entire event is only a few milliseconds </li></ul></ul><ul><li>Events in generation and transmission of an action potential identical between neurons and skeletal muscle cells </li></ul>
  52. 52. ACTION POTENTIALS
  53. 53. ACTION POTENTIALS <ul><li>Not all local depolarizations produce action potentials </li></ul><ul><li>Depolarization must reach threshold values </li></ul><ul><ul><li>Brief, weak stimuli produce subthreshold depolarizations that are not translated into nerve impulses </li></ul></ul><ul><ul><li>Stronger threshold stimuli produce depolarizing events </li></ul></ul>
  54. 54. ACTION POTENTIALS <ul><li>Action potential is all-or-nothing phenomenon </li></ul><ul><ul><li>Happens completely or doesn’t happen </li></ul></ul><ul><li>Independent of stimulus strength once generated </li></ul><ul><ul><li>Strong stimuli generate more impulses of the same strength per unit time </li></ul></ul><ul><ul><li>Intensity is determined by number of impulses per unit time </li></ul></ul>
  55. 55. ACTION POTENTIALS <ul><li>Refractory Periods </li></ul><ul><li>Neuron cannot respond to a second stimulus while the Na + channels are still open from previous stimulus </li></ul><ul><ul><li>This period of time is termed the “absolute refractory period” </li></ul></ul><ul><li>“ Relative refractory period” follows the absolute refractory period </li></ul><ul><ul><li>Repolarization is occurring </li></ul></ul><ul><ul><li>Threshold for impulse generation is elevated </li></ul></ul><ul><ul><ul><li>Only strong stimuli can generate impulses </li></ul></ul></ul>
  56. 56. ACTION POTENTIALS <ul><li>Conduction Velocities </li></ul><ul><li>Conduction velocities of neurons vary widely </li></ul><ul><li>Rate of impulse propagation dependent upon </li></ul><ul><ul><li>Axon diameter </li></ul></ul><ul><ul><ul><li>Larger axons conduct impulses faster </li></ul></ul></ul><ul><ul><li>Degree of myelination </li></ul></ul><ul><ul><ul><li>Myelin sheath dramatically increases rate of propagation </li></ul></ul></ul><ul><ul><ul><ul><li>Myelin acts as an insulator to prevent almost all leakage from axon </li></ul></ul></ul></ul>
  57. 57. ACTION POTENTIALS <ul><li>Multiple Sclerosis (MS) </li></ul><ul><li>Autoimmune disease mainly affecting young adults </li></ul><ul><li>Myelin sheaths in CNS are gradually destroyed </li></ul><ul><li>Interferes with impulse conduction </li></ul><ul><ul><li>Visual disturbances, muscle control problems, speech disturbances, etc. </li></ul></ul><ul><li>Some modern treatments showing some promise in delaying problems </li></ul>
  58. 58. NERVE FIBERS <ul><li>Classified based on </li></ul><ul><ul><li>Diameter </li></ul></ul><ul><ul><li>Degree of myelination </li></ul></ul><ul><ul><li>Conduction speed </li></ul></ul>
  59. 59. NERVE FIBER CLASSIFICATION <ul><li>Group A fibers </li></ul><ul><ul><li>Largest diameter </li></ul></ul><ul><ul><li>Thick myelin sheaths </li></ul></ul><ul><ul><li>Conduct impulses at high speeds (> 300 mph) </li></ul></ul><ul><ul><li>Mostly somatic sensory ad motor fibers serving skin, skeletal muscles, and joints </li></ul></ul><ul><li>Group B fibers </li></ul><ul><ul><li>Intermediate diameter </li></ul></ul><ul><ul><li>Lightly myelinated </li></ul></ul><ul><ul><li>Transmit impulses at moderate speeds (40 mph) </li></ul></ul><ul><li>Group C fibers </li></ul><ul><ul><li>Smallest diameter </li></ul></ul><ul><ul><li>Unmyelinated </li></ul></ul><ul><ul><li>Transmit impulses comparatively slowly (2 mph or less) </li></ul></ul>
  60. 60. Nerve Fiber Classification <ul><li>General classification scheme (Erlanger-Gasser): </li></ul><ul><ul><li>A fibers: Myelinated </li></ul></ul><ul><ul><ul><li>Subtypes:  some overlap in ranges  </li></ul></ul></ul><ul><ul><ul><li>Fastest conducting and largest diameter –  m/sec,  </li></ul></ul></ul><ul><ul><ul><li>“ A” often dropped: alpha motor neuron </li></ul></ul></ul><ul><ul><li>B fibers: Slower myelinated (seldom used) </li></ul></ul><ul><ul><li>C fibers: Unmyelinated </li></ul></ul><ul><ul><ul><li>Slower conducting than As and smallest diameter (0.5 m/sec, 0.5  ) </li></ul></ul></ul>
  61. 61. Nerve Fiber Classification <ul><li>Sensory nerve classification (Lloyd-Hunt): </li></ul><ul><ul><li>I, II, III fibers: Myelinated </li></ul></ul><ul><ul><ul><li>Subtypes: Ia, Ib  </li></ul></ul></ul><ul><ul><ul><li>Fastest conducting and largest diameter – Ia </li></ul></ul></ul><ul><ul><li>IV fibers: Unmyelinated </li></ul></ul><ul><ul><ul><li>Slower conducting than IIIs and smallest diameter </li></ul></ul></ul>
  62. 62. SYNAPSE <ul><li>Junction mediating information transfer from one neuron to another neuron or an effector cell </li></ul><ul><li>Axodendritic synapses </li></ul><ul><ul><li>Axonal endings  dendrites of second neuron </li></ul></ul><ul><li>Axosomatic synapses </li></ul><ul><ul><li>Axonal endings  cell body of neuron </li></ul></ul><ul><li>Presynaptic neuron </li></ul><ul><ul><li>Conducts impulses toward the synapse </li></ul></ul><ul><li>Postsynaptic neuron </li></ul><ul><ul><li>Transmits impulse away from the synapse </li></ul></ul>
  63. 63. SYNAPSE TYPES <ul><li>Electrical Synapses </li></ul><ul><li>Less common than chemical synapses </li></ul><ul><li>Correspond to gap junctions found elsewhere </li></ul><ul><ul><li>Cytoplasm of adjacent neurons connected through protein channels </li></ul></ul><ul><ul><li>Ions flow directly between neurons </li></ul></ul><ul><ul><li>Neurons are “electrically coupled” </li></ul></ul><ul><li>Transmission across synapse is very rapid </li></ul>
  64. 64. SYNAPSE TYPES <ul><li>Chemical Synapses </li></ul><ul><li>Specialized for release & reception of neurotransmitters </li></ul><ul><li>Two parts </li></ul><ul><ul><li>Axonal terminal of presynaptic neuron </li></ul></ul><ul><ul><ul><li>Contains numerous synaptic vesicles filled with neurotransmitter molecules </li></ul></ul></ul><ul><ul><li>Neurotransmitter receptor region </li></ul></ul><ul><ul><ul><li>Present on dendrite or cell body of postsynaptic neuron </li></ul></ul></ul><ul><li>Separated by synaptic cleft </li></ul><ul><ul><li>Remember this stuff in muscles? </li></ul></ul>
  65. 65. SYNAPSE <ul><li>Nerve impulse reaches axonal terminal </li></ul><ul><li>Voltage-gated Ca 2+ channels open in axon </li></ul><ul><ul><li>Ca 2+ enters presynaptic neuron </li></ul></ul><ul><li>Neurotransmitter is released via exocytosis </li></ul><ul><ul><li>Vesicles fuse with axonal membrane </li></ul></ul><ul><li>Neurotransmitter binds to postsynaptic receptors </li></ul><ul><li>Ion channels open in postsynaptic membrane </li></ul><ul><ul><li>Result is excitation or inhibition </li></ul></ul>
  66. 66. SYNAPSE <ul><li>Binding of neurotransmitter to its receptor is reversible </li></ul><ul><li>Permeability affected as long as neurotransmitter is bound to its receptor </li></ul><ul><li>Neurotransmitters do not persist in the synaptic cleft </li></ul><ul><ul><li>Degraded by enzymes associated with postsynaptic membrane </li></ul></ul><ul><ul><li>Reuptake by astrocytes or presynaptic terminal </li></ul></ul><ul><ul><li>Diffusion of neurotransmitters away from synapse </li></ul></ul>
  67. 67. SYNAPSE <ul><li>Transmission of impulses along axon can be very fast </li></ul><ul><ul><li>Up to 300 mph (150 m/s) </li></ul></ul><ul><li>Transmission of a signal across a synapse is slow in comparison </li></ul><ul><ul><li>Leads to “synaptic delay” </li></ul></ul><ul><ul><li>~0.3 0 5.0 milliseconds </li></ul></ul><ul><ul><li>Rate-limiting step of neural transmission </li></ul></ul><ul><ul><li>Transmission along multisynaptic pathways is slower than along pathways with fewer synapses </li></ul></ul>
  68. 68. SYNAPSE <ul><li>Postsynaptic Potentials </li></ul><ul><li>Many receptors present on postsynaptic membranes open ion channels </li></ul><ul><ul><li>Ligand-gated channels </li></ul></ul><ul><ul><li>Electrical signal converted to chemical signal converted to electrical signal </li></ul></ul><ul><ul><li>Graded potential is produced </li></ul></ul><ul><ul><ul><li>Magnitude is dependent upon amount of neurotransmitter released </li></ul></ul></ul><ul><ul><ul><li>Action potential may be produced </li></ul></ul></ul><ul><ul><li>Either excitatory or inhibitory </li></ul></ul>
  69. 69. SYNAPSE <ul><li>Excitatory Synapses </li></ul><ul><li>Neurotransmitter binding causes depolarization </li></ul><ul><ul><li>Single type of channel opens in membrane </li></ul></ul><ul><ul><li>Na + and K + simultaneously diffuse through the membrane in opposite directions </li></ul></ul><ul><ul><li>Na + influx exceeds K + efflux </li></ul></ul><ul><ul><li>Net depolarization occurs </li></ul></ul><ul><ul><li>Local graded depolarization events formed </li></ul></ul><ul><ul><ul><li>“ Excitatory postsynaptic potential (EPSP)” </li></ul></ul></ul><ul><ul><ul><li>May trigger an action potential at axon hillock </li></ul></ul></ul><ul><ul><ul><ul><li>Voltage-gated channels at hillock open, etc. </li></ul></ul></ul></ul>
  70. 70. SYNAPSE <ul><li>Inhibitory Synapses </li></ul><ul><li>Neurotransmitter binding reduces a postsynaptic neuron’s ability to generate an action potential </li></ul><ul><ul><li>Increased permeability to K + and Cl - , not Na + </li></ul></ul><ul><ul><li>Postsynaptic neuron becomes less likely to fire </li></ul></ul><ul><ul><li>“ Inhibitory postsynaptic potential (IPSP)” </li></ul></ul>
  71. 71. SYNAPSE <ul><li>Summation </li></ul><ul><li>A single ESPS cannot induce an action potential </li></ul><ul><ul><li>Requires multiple axonal termini firing in concert </li></ul></ul><ul><ul><ul><li>Hundreds or thousands of EPSPs act together </li></ul></ul></ul><ul><ul><ul><ul><li>“ Summation” </li></ul></ul></ul></ul><ul><li>Two types of summation </li></ul><ul><ul><li>Temporal summation </li></ul></ul><ul><ul><ul><li>One or more neurons transmit in rapid succession </li></ul></ul></ul><ul><ul><li>Spatial summation </li></ul></ul><ul><ul><ul><li>Simultaneous stimulation by numerous termini from one or more neurons </li></ul></ul></ul><ul><ul><li>(Both EPSPs and IPSPs summate) </li></ul></ul>
  72. 72. SYNAPSE <ul><li>Synaptic Potentiation </li></ul><ul><li>Repeated or continuous use of a synapse enhances presynaptic neuron’s ability to excite </li></ul><ul><ul><li>Larger postsynaptic potentials produced </li></ul></ul><ul><ul><li>“ Synaptic potentiation” </li></ul></ul><ul><ul><ul><li>Greater [Ca++] inside presynaptic terminals </li></ul></ul></ul><ul><ul><ul><li>More neurotransmitter released </li></ul></ul></ul><ul><ul><ul><li>Larger EPSPs produced </li></ul></ul></ul>
  73. 73. SYNAPSE <ul><li>Presynaptic Inhibition </li></ul><ul><li>Release of excitatory neurotransmitter can be inhibited by activity of another neuron </li></ul><ul><ul><li>Less neurotransmitter released and bound </li></ul></ul>
  74. 74. NEUROTRANSMITTERS <ul><li>More than fifty neurotransmitters identified </li></ul><ul><li>Most neurons make two or more </li></ul><ul><ul><li>Can be released singly or together </li></ul></ul><ul><li>Classification by Structure </li></ul><ul><li>Acetylcholine (ACh) </li></ul><ul><li>Biogenic amines </li></ul><ul><li>Amino acids </li></ul><ul><li>Peptides </li></ul><ul><li>ATP </li></ul><ul><li>Dissolved gases </li></ul><ul><li>Classification by Function </li></ul><ul><li>Excitatory/Inhibitory </li></ul><ul><li>Direct/Indirect </li></ul>
  75. 75. NEURAL INTEGRATION <ul><li>Neurons function in groups, not singly </li></ul><ul><li>These various components must interact </li></ul><ul><li>Multiple levels of neural integration </li></ul>
  76. 76. NEURONAL POOLS <ul><li>Neurons in CNS are organized into pools </li></ul><ul><ul><li>Functional groups </li></ul></ul><ul><ul><li>Integrate incoming information </li></ul></ul><ul><ul><li>Forward processed information </li></ul></ul>
  77. 77. NEURONAL POOLS <ul><li>Simple Neuronal Pool </li></ul><ul><li>Incoming fiber branches profusely upon entering pool </li></ul><ul><li>EPSPs induced in multiple postsynaptic neurons </li></ul><ul><li>EPSPs exceed threshold in some neurons </li></ul><ul><ul><li>Mainly those with multiple synaptic contacts </li></ul></ul><ul><li>EPSPs do not exceed threshold in some neurons </li></ul><ul><ul><li>Mainly those with fewer synaptic contacts </li></ul></ul><ul><ul><li>Some close to threshold </li></ul></ul><ul><ul><ul><li>“ Facilitated zone” </li></ul></ul></ul>
  78. 78. TYPES OF CIRCUITS <ul><li>Patterns of synaptic connections in neuronal pools are called circuits </li></ul><ul><ul><li>Determine neuronal pool’s functional capabilities </li></ul></ul><ul><li>Four basic circuit patterns </li></ul><ul><ul><li>Diverging circuits </li></ul></ul><ul><ul><li>Converging circuits </li></ul></ul><ul><ul><li>Reverberating (oscillating) circuits </li></ul></ul><ul><ul><li>Parallel after-discharge circuits </li></ul></ul>
  79. 79. TYPES OF CIRCUITS <ul><li>Diverging (Amplifying) Circuit </li></ul><ul><li>One incoming fiber triggers responses in ever-increasing numbers of neurons </li></ul><ul><li>Common in both sensory and motor systems </li></ul>
  80. 80. TYPES OF CIRCUITS <ul><li>Converging Circuits </li></ul><ul><li>Pool receives inputs from several neurons </li></ul><ul><li>Circuit has “funneling” effect </li></ul><ul><li>Common in sensory and motor systems </li></ul>
  81. 81. TYPES OF CIRCUITS <ul><li>Reverberating (Oscillating) Circuits </li></ul><ul><li>Incoming signal travels through chain of neurons </li></ul><ul><li>Each neuron makes synapses with neurons upstream in the pathway </li></ul><ul><li>Involved in rhythmic activities (e.g., breathing) </li></ul>
  82. 82. TYPES OF CIRCUITS <ul><li>Parallel After-Discharge Circuits </li></ul><ul><li>Incoming fiber stimulated parallel neuron arrays </li></ul><ul><li>Parallel arrays ultimately stimulate a common output cell </li></ul><ul><ul><li>Create prolonged burst of impulses </li></ul></ul><ul><li>Involved in complex mental processing </li></ul>
  83. 83. PROCESSING PATTERNS <ul><li>Serial input processing </li></ul><ul><ul><li>Input travels along one pathway to a specific destination </li></ul></ul><ul><ul><li>All-or-nothing function of system </li></ul></ul><ul><ul><ul><li>e.g., reflexes </li></ul></ul></ul><ul><li>Parallel input processing </li></ul><ul><ul><li>Inputs are segregated into multiple pathways </li></ul></ul><ul><ul><ul><li>Integrated in different CNS regions </li></ul></ul></ul><ul><ul><ul><li>Different circuits do different things with input </li></ul></ul></ul><ul><ul><ul><ul><li>Not repetitious </li></ul></ul></ul></ul>

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