Chapter 11

1. Chapter 11 Fundamentals of the Nervous System and Nervous Tissue J.F. Thompson, Ph.D. & J.R. Schiller, Ph.D. & G. Pitts, Ph.D.

2. The Nervous System • The Nervous System is the rapid control system of the body • There are two anatomical divisions to the Nervous System: • The Central Nervous System (CNS) • The Peripheral Nervous System (PNS) • They work together as a single coordinated whole

3. The Functions of the Nervous System • There are three interconnected functions: • sensory input • from millions of specialized receptors • receive stimuli • integration • process stimuli • interpret stimuli • motor output • cause response • at many effector organs

4. Organization of the Central Nervous System • the Brain and Spinal Cord • process & integrate information, store information, determine emotions • initiate commands for muscle contraction, glandular secretion and hormone release (regulate and maintain homeostasis) • connected to all other parts of the body by the Peripheral Nervous System (PNS)

5. Organization of the Peripheral NS • anatomical connections • spinal nerves are connected to the spinal cord • cranial nerves are connected to the brain • two functional subdivisions • sensory (afferent) division • somatic afferents - skin, skeletal muscle, tendons, joints • special sensory afferents • visceral afferents - visceral organs • motor (efferent) division • motor (efferent) neurons • muscles/glands

6. Organization of the PNS (continued) • motor (efferent) division has two parts: • Somatic Nervous System (SNS) • voluntary motor neurons • output to skeletal muscles • Autonomic Nervous System (ANS) • involuntary visceral motor neurons • output to smooth muscle, cardiac muscles and to glands • two cooperative components: • sympathetic division • parasympathetic division

7. Autonomic Nervous System • Sympathetic Division – for muscular exertion and for “fight or flight” emergencies • Parasympathetic Division – for metabolic/ physiologic “business as usual” (“feed or breed”)

8. Nervous Tissue • Review the microanatomy of nervous tissue in lab and in the PPT with audio: CH11 Histology of Nervous Tissue • Nerve cell physiology is primarily a cell membrane phenomenon • Information transmission differs between dendrites and axons

9. Neuron Processes - Dendrites • short, tapering, highly branched extensions of the soma • not myelinated • contain some cell organelles • receptive—initiate and transmit graded potentials (not action potentials) to the cell body

10. Neuron Processes - Axons • A single process that transmits action potentials from the soma • Originates from a cone-shaped “axon hillock” • May be long (1 meter) or short (<1 mm) • long axons called nerve fibers • Up to 10,000 terminal branches • each with an axon terminal that synapses (joins) with a neuron or an effector (muscle or gland cell)

11. Axons (continued) • Axoplasm: the cytoplasm of the axon • Axolemma: the cell membrane of the axon, specialized to initiate and conduct action potentials (nerve impulses) • initiated at the axon hillock (trigger zone), travels to the axon terminal • causes release of neurotransmitter from terminal • neurotransmitters can excite or inhibit • transfers a control message to other neurons or effector cells

12. Histology of Neurons – Myelin Sheath • lipid-rich, segmented covering on axons • most larger, longer axons are myelinated • dendrites are never myelinated • myelin protects & electrically insulates the axon • increases the speed of nerve impulses • myelinated fibers conduct impulses 10-150x faster than unmyelinated fibers • 150 m/sec vs. 1 m/sec

13. Myelinating Cells • neurolemmocytes (Schwann cells) in the Peripheral NS • oligodendrocytes in the Central NS

14. Myelination • occurs during fetal development and the first year of life • each myelinating cell wraps around an axon up to 100 times, squeezing its cytoplasm and organelles to the periphery • myelin sheath: multiple layers of the cell membrane • neurolemma (sheath of Schwann): outer layer containing the bulk of the cytoplasm and cell organelles

15. Myelinated and Unmyelinated Axons • Myelinated Fibers • Myelin sheath • neurofibril nodes (Nodes of Ranvier) periodic gaps in the myelin sheath between the neurolemmocytes • Unmyelinated Fibers • surrounded by neurolemmocytes but no myelin sheath present • neurolemmocytes may enclose up to 15 axons (unmyelinated fibers) neurolemmocytes guide regrowth of neuron processes after injury

16. Myelination In the Central NS • Gray matter - unmyelinated cell bodies & processes • White matter – myelinated processes in various fiber tracts

17. Classification of Neurons • Structural: based on the number of processes extending from the cell body • Functional: based on the direction (location) of nerve impulses We will focus on functional classification

18. Afferent (= Sensory) Neurons • afferent = towards CNS • nerve impulses from specific sensory receptors (touch, sight, etc.) are transmitted to the spinal cord or brain (CNS) • afferent neuron cell bodies are located outside the CNS in ganglia

19. Efferent (= Motor) Neurons • efferent = away from CNS • nerve impulses from CNS (brain and spinal cord) are transmitted to effectors (muscles, endocrine and exocrine glands) • efferent neuron cell bodies are located inside the CNS

20. Association Neurons (= Interneurons) • carry nerve impulses from one neuron to another • 99% of the neurons in the body are interneurons • most interneurons are located in the CNS

21. Neurophysiology - Definitions • voltage • the measure of potential energy generated by separated charges • always measured between two points – the inside versus the outside of the cell • referred to as a potential - since the charges (ions) are separated there is a potential for the charges (ions) to move along the charge gradient

22. Neurophysiology - Definitions • current • the flow of electrical charge from one point to another • in the body, current is due to the movement of charged ions • resistance • the prevention of the movement of charges (ions) • caused by the structures (membranes) through which the charges (ions) have to flow

23. Neurophysiology - Basics • Cell interior and exterior have different chemical compositions • Na+/K+ ATPase pumps change the ion concentrations • a semi-permeable membrane allows for separation of ions • Ions attempt to reach electrochemical equilibrium • two forces power the movement of ions • individual ion concentrations (chemical gradients) • net electrical charge (overall charge gradient) • the balance between concentration (chemical) gradients and the electrical gradient known as the electrochemical equilibrium • the external voltage required to balance the concentration gradient is the equilibrium (voltage) potential

24. Neurophysiology - Membrane Ion Channels • regulate ion movements across cell membrane • each is specific for a particular ion or ions • many different types • may be passive (leaky) • may be active (gated) • gate status is controlled • gated channels are regulated by signal chemicals or by other changes in the membrane potential (voltage potential)

25. Resting Membrane Potential (RMP) • electrical charge gradient associated with outer cell membrane • present in all living cells • the cytoplasm within the cell membrane is negatively charged due to the charge disequilibrium concentrations of cations and anions on either side of the membrane • RMP varies from about -40 to -90 millivolts (a net negative charge inside relative to a net positive charge outside the cell)

26. Resting Membrane Potential (cont.) • RMP is similar to a battery • stores an electrical charge and can release the charge • 2 main reasons for this: • ion concentrations on either side of the plasma membrane are due to the action of the Na+/K+ ATPase pumps • primarily, Na+ and Cl- are outside; the membrane is polarized • primarily, K+, Cl-, proteins- and organic phosphates- are inside • plasma membrane has limited permeability to Na+ and K+ ions

27. Resting Membrane Potential (cont.) • Resting conditions • Na+/K+ ATPase pumps 3 Na+ ions out and 2 K+ ions in per ATP hydrolysis – opposing their concentration gradients • concentration gradient drives Na+ to go into the cell • concentration gradient drives K+ to go out of the cell • if the cell membrane were permeable to Na+ and K+ ions, then Na+ and K+ ions would diffuse along their electrical and chemical gradients and would reach equilibrium • if the cell was at equilibrium in terms of ion concentrations and charge, their would be no potential energy available for impulse transmission

28. Resting Membrane Potential (cont.) • Neuron Membrane at rest is polarized • the cytoplasm inside is negatively charged relative to the outside • the net negative charge in the cytoplasm attracts all cations to the inside • some Na+ leaks in, despite limited membrane permeability • Na+-K+ ATPase keeps working to pump 3 Na+ ions out and 2 K+ ions in, opposing the two concentration gradients (for Na+ and K+)

29. Resting Membrane Potential (cont.) • Here is the electrochemical gradient at rest: the resting potential

30. Membrane Potentials As Signals • cells use changes in membrane potential (voltage) to exchange information • voltage changes occur by two means: • changing the membrane permeability to an ion; or • changing the ion concentration on either side of the membrane • these changes are made by ion channels • passive channels – leaky: K+ • active channels: • chemically gated – by neurotransmitters • voltage gated

31. Types of Membrane Potentials • graded potentials • graded = different levels of strength • dependent on strength of the stimulus • action potentials • in response to graded potentials of significant strength • signal over long distances • all or nothing

32. Types of Membrane Potentials • graded potentials and action potentials may be either: • hyperpolarizing • increasing membrane polarity • making the inside more negative • depolarizing • decreasing membrane polarity • making the inside less negative = more positive

33. Properties of Action Potentials • a nerve impulse (action potential) is generated in response to a threshold graded potential • depolarization • change in the membrane polarization • stimuli reach a threshold limit and open voltage-gated Na+ channels • Na+ ions rush into the cell  down the Na+ concentration and electrical gradients • the cytoplasm inside the cell becomes positive • reverses membrane potential to +30 mV • local anesthetics prevent opening of voltage-gated Na+ channels - prevent depolarization

34. Sequence of Events in Action Potentials • Resting membrane potential

35. Sequence of Events in Action Potentials • Depolarization • stimulus strength reaches threshold limit • voltage gated Na+ channels open • Na+ flows into the cytoplasm • More V-gated Na+ channels open [positive feedback]

36. Sequence of Events in Action Potentials • Repolarization • voltage gated K+ channels open • voltage gated Na+ channels close

37. Sequence of Events in Action Potentials • Hyperpolarization • gated Na+ channels are reset to closed • membrane remains hyperpolarized until K+ channels close, causing the relative refractory period

38. Repeat the process:

39. Sequence of Events in Action Potentials • Resting membrane potential

40. Sequence of Events in Action Potentials • Depolarization • stimulus strength reaches threshold limit • voltage gated Na+ channels open • Na+ flows into the cytoplasm • More V-gated Na+ channels open [positive feedback]

41. Sequence of Events in Action Potentials • Repolarization • voltage gated K+ channels open • voltage gated Na+ channels close

42. Sequence of Events in Action Potentials • Hyperpolarization • gated Na+ channels are reset to closed • membrane remains hyperpolarized until K+ channels close, causing the relative refractory period

43. The All-or-None Principle • stimuli/neurotransmitters arrive and open some of the chemically-gated Na+ channels • if stimuli reach the threshold level  depolarization occurs • voltage-gated Na+ channels open • an Action Potential is generated which is constant and at maximum strength • if stimuli do not reach the threshold level  nothing happens

44. Repolarization • Re-establishing the resting membrane polarization state • threshold depolarization opens Na+ channels • Na+ ions flow inward, making the cell interior more positive • a few milliseconds later, K+ channels also open • K+ channels open more slowly and remain open longer • K+ ions flow out along its concentration and charge gradients • carries positive (+) charges out, making the cell interior more negative (-) • Ion movements drive the membrane potential back toward resting membrane potential value • Na+/K+ ATPase continue pumping ions, adjusting levels back to resting equilibrium levels • hyperpolarization – briefly the exterior of the membrane is more negative than resting potential voltage level

45. Refractory Periods Many physiologists consider this to be the start of the absolute refractory period • Absolute Refractory Period • the time period during which second AP cannot be initiated • due to closure of voltage-gated Na+ channels • the voltage-gated Na+ channels must be reset before the membrane can respond to the next stimulus

46. Refractory Periods • Relative Refractory Period • The time period during which a second AP can be initiated with a suprathreshold stimulus • K+ channels are open, Na+ channels are closed • the membrane is still hyperpolarized

47. Propagation of an Action Potential • the movement of an Action Potential down an unmyelinated axon • a local electrochemical current, a flow of charged ions • influx of sodium ions • attraction of positive charges for negative area of membrane nearby • depolarizes nearby membrane – opening V-gated Na+ channels

48. Propagation of an Action Potential • destabilizing the adjacent membrane makes the Action Potential self-propagating and self-sustaining • the Action Potential renews itself at each region of the membrane – a relatively slow process because so much is happening at the molecular level

49. Conduction Velocity • physical factors may influence impulse conduction • heat increases conduction velocity • cold decreases conduction velocity • 2 structural modifications can increase impulse velocity: • increase neuron diameter - decreases resistance • insulate the neuron - myelin sheath • myelinated fibers may conduct as rapidly as 150 m/sec • unmyelinated may conduct as slowly as 0.5 m/sec

50. Saltatory Conduction • not a continuous region to region depolarization • instead, a “jumping” depolarization • myelinated axons transmit an Action Potential differently • the myelin sheath acts as an insulator preventing ion flows in and out of the membrane • neurofibral nodes (node of Ranvier) interrupt the myelin sheath and permit ion flows at the exposed locations on the axon membrane • the nodes contain a high density of voltage-gated Na+ channels