The Nervous System

1. The Nervous System • Three Functions • Sensory Input (Afferent) **Affect • Integration (Processing/Interpretation) • Motor Output (Efferent) **Effect

3. Nervous System Organization • Central Nervous System (CNS) • Brain • Spinal Cord • Peripheral Nervous System (PNS) • Afferent Division (Sensory) • Efferent Division (Motor)

4. PNS Afferent (Sensory) • Somatic afferent fibers • From skin, skeletal muscles and joints • Visceral afferent fibers • From internal organs (viscera)

5. PNS Efferent (Motor) • Somatic n.s. – impulses to skeletal muscles a.k.a. voluntary ns • Autonomic n.s. – visceral motor fibers to smooth muscles, cardiac muscle, & glands a.k.a. involuntary ns • Sympathetic n.s. (“fight or flight”) = stimulate • Parasympathetic n.s. (“rest and repose”) = inhibit

8. NS Cell Makeup • Neurons – functional transmission cells • Neuroglia – Supporting cells that surround neurons a.k.a. glial cells or “nerve glue” • CNS neuroglia • Astrocytes • Microglia • Ependymal cells • Oligodendrocytes • PNS neuroglia • Satellite cells • Schwann cells

10. Neuroglia • Astrocytes - – most abundant • anchor to BV’s, assist nutrient transfer • glucose uptake, lactic acid delivery • guide migrating “young” neurons • synapse formation • capillary permeability • “mop up” K+ and recapture neurotransmitters

11. Cont. • Microglia – “thorny” processes • neuron “health detectors” – transform to macrophages • Ependymal cells – “wrapping” • squamous to columnar shape + cilia in central cavities of the brain and spinal cord • Permeable barrier between CSF and tissue fluid of CNS • Oligodendrocytes – • wrap the thick nerve fibers of the CNS to make insulated coverings = myelin sheaths

12. Motor Neuron

13. Neurons • A.k.a. nerve cells • Have extreme longevity – up to 100+ years! • Essentially amitotic = cannot divide/regen. • Have high metabolic rate and need continuous glucose and oxygen • Have two major anatomical structures • Cell body • Processes • Axons • Dendrites

14. Axons • Transmitting portion – Action Potentials (AP’s) (conducting component) • Anterograde movement • Retrograde movement (abnormal w/ bacterial/viral agents) • Profuse branching at terminal end (10,000 +) • Knob-like ends on the terminal branches (secretory component – neurotransmitters - NT’s) • Axonal terminals (or) • Synaptic knobs (or) • Boutons

16. Myelin Sheath & Neurilemma • Whitish fatty protein that is segmented • Myelinated nerves conduct rapidly - larger • Unmyelinated nerves conduct slowly- finer • Neurilemma is the “husk” or external part of the Schwann cell • Nodes of Ranvier

18. Classification of Neurons • Structural • Multipolar • Bipolar • Unipolar • Functional • Sensory / Afferent • Motor / Efferent • Interneurons

19. Neurophysiology • Highly irritable • Electrical impulse generated and conducted = AP’s • Voltage or potential difference measured in mV and generally a “resting” membrane of a neuron is ~ -70mV • Membrane Ions channels: “leakage/passive” and “gated/active” • Chemical (ligand) gated – chemical stimuli • Voltage-gated – electrical stimuli • Mechanically – distortion stimuli

21. Resting Membrane Potential

22. Resting Membrane Potential • - 70 mV across the membrane (varies - 40 to - 90mV) when the membrane is polarized • Negative sign means inside (cytoplasmic side) is negatively charged • Charge is based on differences in ionic concentrations in intra and extra-cellular fluids, and differences in permeability • K+ is the most important ion in generating membrane potential

24. Membrane Potentials • Changes in these is involved with receiving, integrating, and sending information. • Caused by: • Anything altering ion permeability • Anything altering ion concentrations on either side of the membrane. • Produces either: • Graded potentials – over short distances • Action potentials – over long distances

25. Cont. • Depolarization – relative to “resting” it is less negative/more positive (closer to “0”) on the inside of the neuron – which increases the probability of producing a nerve impulse • Hyperpolarization – increased membrane potential, or more negative than resting potential – which decreases the probabilility of a nerve impulse.

27. Graded Potentials

29. Action Potentials (AP’s) • Principal form of neuron communication only in excitable membranes of neurons and muscle cells • Brief reversal of membrane potential from -70 to +30 mV • Depolarization followed by repolarization phase and often a hyperpolarization period (msec’s) • AP’s are also called nerve impulses and only axons can generate one. • Stimulus changes permeability via voltage-gated channels on the axon

30. Generating AP’s • Three overlapping membrane permeability changes by opening and closing active ion gates • Resting State: Voltage-gated Na/K+ channels closed • Depolarizing phase: Increase in Na+ permeability and reversal of membrane potential – Na+ influx causes depolarization until threshold (-55 to -50mV) • Repolarizing phase: a) Decrease in Na+ permeability b) w/ increase in K+ permeability • Hyperpolarization: K+ permeability continues to produce undershoot

31. Action Potential: Resting State • Na+ and K+ channels are closed • Leakage accounts for small movements of Na+ and K+ • Each Na+ channel has two voltage-regulated gates • Activation gates – closed in the resting state • Inactivation gates – open in the resting state Figure 11.12.1

32. Action Potential: Depolarization Phase • Na+ permeability increases; membrane potential reverses • Na+ gates are opened; K+ gates are closed • Threshold – a critical level of depolarization (-55 to -50 mV) • At threshold, depolarization becomes self-generating Figure 11.12.2

33. Action Potential: Repolarization Phase • Sodium inactivation gates close • Membrane permeability to Na+ declines to resting levels • As sodium gates close, voltage-sensitive K+ gates open • K+ exits the cell and internal negativity of the resting neuron is restored Figure 11.12.3

34. Action Potential: Hyperpolarization • Potassium gates remain open, causing an excessive efflux of K+ • This efflux causes hyperpolarization of the membrane (undershoot) • The neuron is insensitive to stimulus and depolarization during this time Figure 11.12.4

35. Action Potential: Role of the Sodium-Potassium Pump • Repolarization • Restores the resting electrical conditions of the neuron • Does not restore the resting ionic conditions • Ionic redistribution back to resting conditions is restored by the sodium-potassium pump

36. Propagation of AP’s • Process in unmyelinated nerves: • Away from its point of origin toward axon terminals and then is self-propagating • Ea. segment repolarizes - restores resting potential • Process in myelinated nerves: • Saltatory conduction • Propagation of nerve impulse is a better term to use than nerve impulse conduction

40. Threshold & “All-or-None” • Not all local (graded) potentials lead to AP’s • Reached when outward K+ = inward Na+ movement • At threshold either Na+ gates open with more Na+ entering or close with more K+ leaving and return to resting potential • Stronger stimuli cause threshold to be reached and begins positive feedback cycle • The AP either happens or it does not

41. Stimulus Intensity • AP’s are independent of stimulus strength, therefore the RATE of stimuli allow for the CNS to interpret intensity (i.e. more painful)

43. Refractory Period • When an AP is being generated it can’t respond to another stimulus to create another AP = the absolute refractory period • The relative refractory period follows the absolute while Na+ gates are still closed and neuron is repolarizing. • A very strong stimulus in the relative period CAN cause another AP to be initiated

45. Conduction Velocity • Axon diameter – larger usually means faster, due to less resistance • Degree of myelination a) Unmyelinated develop AP’s in adjoining segments of a neuron, thus are slow moving b) Myelinated are “insulated” by myelin and only allow current to pass at the nodes of Ranvier where voltage-gated channels are concentrated, thus are fast moving & are termed saltatory conduction (Abnormal = MS)

46. Saltatory Conduction

47. Multiple Sclerosis (MS) • An autoimmune disease that mainly affects young adults • Symptoms: visual disturbances, weakness, loss of muscular control, and urinary incontinence • Nerve fibers are severed and myelin sheaths in the CNS become nonfunctional scleroses • Shunting and short-circuiting of nerve impulses occurs

48. Multiple Sclerosis: Treatment • The advent of disease-modifying drugs including interferon beta-1a and -1b, Avonex, Betaseran, and Copazone: • Hold symptoms at bay • Reduce complications • Reduce disability

49. Nerve Fiber Classification • Group A = large diameter myelinated found in somatic sensory and motor fibers of the skin muscles and joints (150 m/s) • Group B = lightly myelinated and intermediated diameter found in ANS motor fibers, visceral sensory fibers & smaller somatic sensory fibers (15 m/s) • Group C = smallest and unmyelinated found in similar areas as B fibers (1 m/s)

50. Imbalances • Alcohol, sedatives and anesthetics all impair Na+ permeability = no AP’s • Cold and pressure interrupt blood flow and thus O2 delivery impairing AP generation and thus ability to conduct impulses