NERVOUS SYSTEM

1. NERVOUS SYSTEM

2. NERVOUS FUNCTIONS Body’s master controlling and communicating system Three functions Sensory input Gathers information from sensory receptors Integration Processes and interprets sensory input Motor output Activates effector organs to cause a response

3. ORGANIZATION Two Principal Parts of the System Central nervous system (CNS) Brain and spinal cord Integrating and command center Interprets sensory input Dictates motor responses Peripheral nervous system (PNS) Nerves extending from brain and spinal cord Carry impulses to and from the CNS

4. PERIPHERAL DIVISIONS Two Functional Subdivisions of the PNS Sensory division a.k.a. “afferent division” Nerve fibers conveying impulses to the CNS Somatic afferent fibers convey impulses from the skin, muscles, and joints Visceral afferent fibers convey impulses from visceral organs Motor division a.k.a., “efferent division” Nerve fibers conveying impulses from the CNS

5. MOTOR DIVISIONS Two Parts of the Motor Division Somatic nervous system a.k.a., “voluntary nervous system” Nerve fibers conducting impulses from CNS to skeletal muscles Autonomic nervous system a.k.a., “involuntary nervous system” Nerve fibers regulating the activity of smooth muscles, cardiac muscles, and glands

6. AUTONOMIC DIVISIONS Functional Subdivisions of the Autonomic Nervous System Sympathetic Mobilizes body systems during emergency situations Parasympathetic division Conserves energy Promotes non-emergency functions

7. ORGANIZATION Summary Central nervous system Brain Spinal cord Peripheral nervous system Sensory division Motor division Somatic nervous system Autonomic nervous system Sympathetic division Parasympathetic division

8. HISTOLOGY Nervous system consists mainly of nervous tissue Highly cellular e.g., <20% extracellular space in CNS Two principal cell types Neurons Excitable nerve cells that transmit electrical signals Supporting cells Smaller cells surrounding and wrapping neurons “Neuroglia”

9. NEUROGLIA “Nerve glue” Six types of small cells associated with neurons 4 in CNS 2 in PNS Most have central cell body and branching processes Several functions e.g., Supportive scaffolding for neurons e.g., Electrical isolation of neurons e.g., Neuron health and growth

10. CNS NEUROGLIA Astrocytes Microglia Ependymal cells Oligodendrocytes

11. CNS NEUROGLIA Astrocytes Most abundant and versatile glial cells Numerous processes support branching neurons Anchor neurons to capillary blood supply Guide migration of young neurons Facilitate nutrient delivery to neurons (blood ? glial cell ? neuron) Control chemical environment around neurons Uptake of K+, neurotransmitters Communicate with astrocytes & neurons Gap junctions, Ca2+ surges

12. CNS NEUROGLIA Microglia Small ovoid cells Relatively long “thorny” processes Processes touch nearby neurons “Checking vitals” Migrate toward injured neurons Transform into macrophage Phagocytize microorganisms, debris (Cells of immune system cannot enter the CNS)

13. CNS NEUROGLIA Ependymal Cells Line central cavities of brain and spinal cord Form permeable barrier between cerebrospinal fluid inside these cavities and tissue fluid of CNS tissue Shapes range from squamous to columnar Many are ciliated Beating helps circulate cerebrospinal fluid cushioning brain and spinal cord

14. CNS NEUROGLIA Oligodendrocytes Fewer processes than astrocytes Wrap processes tightly around thicker neuron fibers in CNS “Myelin sheath” Insulating covering

15. PNS NEUROGLIA Satellite cells Schwann cells

16. PNS NEUROGLIA Satellite cells Surround neuron cell bodies within ganglia (A ganglion is a collection of nerve cell bodies outside of the CNS) Function poorly understood

17. PNS NEUROGLIA Schwann cells a.k.a., “Neurolemmocytes” Surround and form myelin sheaths around larger nerve fibers of PNS Functionally similar to oligodendrocytes Vital to regeneration of peripheral nerve fibers

18. NEURONS a.k.a., Nerve cells Structural units of nervous system Billions are present in nervous system Conduct messages throughout body Nerve impulses Extreme longevity Can function optimally for entire lifetime Amitotic Ability to divide is lost in mature cells Cannot be replaced if destroyed Some (very few) exceptions e.g., stem cells present in olfactory epithelium can produce new neurons Stem cell research shows great promise in repairing damaged neurons High metabolic rate Require large amounts of oxygen and glucose

19. NEURONS Generally large, complex cells Structures vary, but all neurons have the same basic structure Cell body Slender processes extending from cell body Plasma membrane is site of signaling

20. NEURON CELL BODY Most neuron cell bodies are located in the CNS Protected by bones of skull or vertebral column Clusters of cell bodies in the CNS are termed “nuclei” Clusters of cell bodies in the PNS are termed “ganglia”

21. NEURON CELL BODY a.k.a., “perikaryon” or “soma” 5 – 140 mm in diameter Transparent spherical nucleus Contains conspicuous nucleolus

22. NEURON CELL BODY Major biosynthetic center of neuron Other usual organelles present ER & ribosomes most active and best developed in body What do they do? Centrioles absent What do centrioles do? Sometimes contains pigment inclusions

23. NEURON CELL BODY Focal point for the outgrowth of neuron processes during embryonic development Some processes receive signals Plasma membrane generally also acts as part of the receptive surface

24. NEURON PROCESSES Extend from the neuron’s cell body CNS contains both neuron cell bodies and their processes Bundles of CNS processes are termed “tracts” PNS consists mainly of neuronal processes Bundles of PNS processes are termed “nerves” Two types of neuron processes Dendrites Axons

25. NEURON PROCESSES Typical Dendrite Short, tapering, diffusely branching extensions Generally hundreds clustering close to cell body Most cell body organelles also present in dendrites Main receptive / input regions Large surface area for receiving signals from other neurons Convey incoming messages toward cell body Short-distance signals are “graded potentials” Not action potentials

26. NEURON PROCESSES Typical Axon Single axon per neuron “Axon hillock” of cell body narrows to form a slender process of uniform diameter Sometimes very short Sometimes very long e.g., axons controlling big toe are 3 – 4 feet long

27. NEURON PROCESSES Typical Axon Single axon may branch along length “Axon collaterals” extend from neurons at ~ 90o angles Usually branches profusely at end 10,000 or more terminal branches is common Distal endings termed “axonal terminals”

28. NEURON PROCESSES Typical Axon Conducting component of neuron Generates nerve impulses Generated at axon hillock / axon junction in motor neurons “Trigger zone” Transmits nerve impulses away from cell body To axonal terminals

29. NEURON PROCESSES Typical Axon Axonal terminals are secretory component of neuron Sequence of events Signal reaches terminals Membranes of vesicles fuse with plasma membrane “Axolemma” Neurotransmitters released Neurotransmitters interact with either other neurons or effector cells Excite or inhibit

30. NEURON PROCESSES Typical Axon Contains most of the same organelles found in dendrites and cell body Lacks ER and Golgi apparatus What do these organelles do? Must rely on cell body to renew what?

31. NEURON PROCESSES Typical Axon Rely on cell body for some molecules Rely on efficient transport mechanisms for delivery Anterograde movement toward axonal terminals e.g., Mitochondria, membrane components, neurotransmitters or enzymes required for neurotransmitter synthesis, etc. Retrograde movement toward cell body e.g., Organelles being returned for recycling

32. NEURON PROCESSES Typical Axon Some viruses and bacterial toxins use retrograde transport to reach the cell body e.g., poliovirus, rabies virus, herpes simplex viruses, tetanus toxin, etc. Such viruses can be used as vehicles for the therapeutic delivery of engineered DNA “Gene therapy”

33. MYELIN SHEATH Whitish, fatty covering of many nerve fibers Particularly those long are large in diameter Protects and electrically insulates fibers Increases speed of nerve impulse transmission Some axons and all dendrites are unmyelinated

34. MYELIN SHEATH In PNS, myelin sheaths formed by Schwann cells Continually wrap around nerve Cytoplasm gradually squeezed from intracellular space Result is many concentric layers of plasma membrane surrounding the axon These plasma membranes contain little protein Some proteins present interlock adjacent membranes Thickness depends on number of wrappings Nucleus and most of cytoplasm exist as a bulge external to the myelin sheath “Neurilemma”

35. MYELIN SHEATH Adjacent Schwann cells on axon do not touch each other Gaps in sheath occur at regular intervals “Nodes of Ranvier” a.k.a., “Neurofibril nodes” Axon collaterals can emerge at these nodes

36. MYELIN SHEATH CNS contains both myelinated and unmyelinated axons Those long are large in diameter are typically myelinated Oligodendrocytes, not Schwann cells, form CNS myelin sheaths Oligodendrocytes possess numerous processes that can coil around numerous (up to 60) axons at once CNS myelin sheaths lack a neurilemma

37. MYELIN SHEATH White matter Regions of the brain and spinal cord containing dense collections of myelinated fibers Gray matter Regions of the brain and spinal cord containing mostly nerve cell bodies and unmyelinated fibers

38. NEURON CLASSIFICATION Structural classification based upon number of processes Multipolar neurons Bipolar neurons Unipolar neurons Functional classification based upon direction nerve impulse travels Sensory (afferent) neurons Motor (efferent) neurons Interneurons (association neurons)

39. NEURON CLASSIFICATION Structural Classification Multipolar neurons Three or more processes Most common neuron type in humans (> 99% of neurons) Bipolar neurons Two processes – axon and dendrite Found only in some special sense organs e.g., retina of eye Act as receptor cells Unipolar neurons Single short process “Pseudounipolar neurons” Originate as bipolar neurons Two processes converge and fuse Process divides into proximal and distal branches Distal process often associated with a sensory receptor “Peripheral process” Central process enters CNS Most are sensory neurons in PNS

40. NEURON CLASSIFICATION Functional Classification Sensory (afferent) neurons Transmit impulses toward CNS From sensory receptors or internal organs Most are unipolar Cell bodies are located outside CNS Motor (efferent) neurons Carry impulses away from CNS Toward effector organs Multipolar Cell bodies generally located in the CNS Interneurons a.k.a., association neurons Lie between motor and sensory neurons in neural pathways Shuttle signals through CNS pathways where integration occurs > 99% of neurons in body Most are multipolar Most are confined within the CNS

41. NEUROPHYSIOLOGY Neurons are highly irritable Responsive to stimuli Response to stimulus is action potential Electrical impulse carried along length of axon Always the same regardless of stimulus The underlying functional feature of the nervous system

42. ELECTRICITY Voltage (V) Measure of potential energy Measured between two points “Potential difference” or simply “potential” Measured in volts or millivolts Current (I) Flow of electrical charge from one point to another Can be used to do work Amount of charge moved depends on voltage & resistance Resistance (R) Hindrance to charge flow Provided by substances through which the current must pass

43. ELECTRICITY Ohm’s Law Current = Voltage / Resistance I = V / R voltage = current * resistance V = I * R

44. ELECTRICITY Electrical currents involve the flow of ions across membranes Resistance to current flow is provided by the plasma membrane Movement of ions across the plasma membrane is regulated by membrane ion channels

45. ION CHANNELS Plasma membranes contain various ion channels Passive channels (leakage channels) Always open Active channels (gated channels) Ligand-gated channels Open when specific chemical binds Voltage-gated channels Open and close in response to membrane potential Mechanically-gated channels Open in response to physical deformation of receptor e.g., touch and pressure receptors

46. ION CHANNELS Channels are specific as to what type of ions are allowed to pass e.g., K+ channels allow only K+ to pass Ions moving through open channels follow their electrochemical gradients Electrical current is generated Voltage changes across the membrane

47. MEMBRANE POTENTIALS A voltage exists across the plasma membrane Due to separation of oppositely charged ions Potential difference in a resting membrane is termed its “resting membrane potential” ~ -70 mV in a resting neuron Membrane is “polarized”

48. MEMBRANE POTENTIALS Resting potential exists across the membrane Majority of Na+ outside of cell Why? Majority of K+ inside of cell Why? Resting membrane Only slightly permeable to Na+ 75 times more permeable to K+ How do these ions cross the membrane?

49. MEMBRANE POTENTIALS Neurons use changes in membrane potentials as signals Used to receive, integrate, and send signals Changes in membrane potentials produced by Anything changing membrane permeability to ions Anything altering ion concentrations Two types of signals Graded potentials Short-distance signals Action potentials Long-distance signals

50. MEMBRANE POTENTIALS Changes in membrane potentials are caused by three events Depolarization Inside of membrane becomes less negative Nerve impulses more likely to be produced Repolarization Membrane returns to resting membrane potential Hyperpolarization Inside of membrane becomes more negative than the resting potential Nerve impulses less likely to be produced

51. MEMBRANE POTENTIALS Graded Potentials Short-lived local changes in membrane potential Either depolarizations or hyperpolarizations Cause current flows that decrease in magnitude with distance Magnitude of potential dependent upon stimulus strength Stronger stimulus ? larger voltage change Larger voltage change ? farther current flows

52. MEMBRANE POTENTIALS Graded Potentials Triggered by change in neuron’s environment Change causes gated ion channels to open Small area of neuron’s plasma membrane becomes depolarized (by this stimulus) Current flows on both sides of the membrane + moves toward – and vise versa

53. MEMBRANE POTENTIALS Graded Potentials Inside cell: + ions move away from depolarized area Outside cell: + ions move toward depolarized area (+ and – ions switch places) Membrane is leaky Most of the charge is quickly lost through membrane Current dies out after traveling a short distance

54. MEMBRANE POTENTIALS Graded Potentials Act as signals over very short distances Important in initiating action potentials

55. MEMBRANE POTENTIALS Action Potentials Principal means by which neurons communicate Brief reversal of membrane potential Total amplitude of ~ 100 mV (-70 ? +30) Depolarization followed by repolarization, then brief period of hyperpolarization Time for entire event is only a few milliseconds Events in generation and transmission of an action potential identical between neurons and skeletal muscle cells

56. ACTION POTENTIALS

57. ACTION POTENTIALS Not all local depolarizations produce action potentials Depolarization must reach threshold values Brief, weak stimuli produce subthreshold depolarizations that are not translated into nerve impulses Stronger threshold stimuli produce depolarizing events

58. ACTION POTENTIALS Action potential is all-or-nothing phenomenon Happens completely or doesn’t happen Independent of stimulus strength once generated Strong stimuli generate more impulses of the same strength per unit time Intensity is determined by number of impulses per unit time

59. ACTION POTENTIALS Refractory Periods Neuron cannot respond to a second stimulus while the Na+ channels are still open from previous stimulus This period of time is termed the “absolute refractory period” “Relative refractory period” follows the absolute refractory period Repolarization is occurring Threshold for impulse generation is elevated Only strong stimuli can generate impulses

60. ACTION POTENTIALS Conduction Velocities Conduction velocities of neurons vary widely Rate of impulse propagation dependent upon Axon diameter Larger axons conduct impulses faster Degree of myelination Myelin sheath dramatically increases rate of propagation Myelin acts as an insulator to prevent almost all leakage from axon

61. ACTION POTENTIALS Multiple Sclerosis (MS) Autoimmune disease mainly affecting young adults Myelin sheaths in CNS are gradually destroyed Interferes with impulse conduction Visual disturbances, muscle control problems, speech disturbances, etc. Some modern treatments showing some promise in delaying problems

62. NERVE FIBERS Classified based on Diameter Degree of myelination Conduction speed

63. NERVE FIBER CLASSIFICATION Group A fibers Largest diameter Thick myelin sheaths Conduct impulses at high speeds (> 300 mph) Mostly somatic sensory ad motor fibers serving skin, skeletal muscles, and joints Group B fibers Intermediate diameter Lightly myelinated Transmit impulses at moderate speeds (40 mph) Group C fibers Smallest diameter Unmyelinated Transmit impulses comparatively slowly (2 mph or less)

64. ION CHANNELS Various chemicals block nerve impulses e.g., alcohol, sedatives, anesthetics, etc. Mechanisms differ, but all reduce membrane permeability to Na+ No Na+ entry ? no action potential Neurons also impaired by cold or continuous pressure Blood supply interrupted O2 delivery compromised

65. SYNAPSE Junction mediating information transfer from one neuron to another neuron or an effector cell Axodendritic synapses Axonal endings ? dendrites of second neuron Axosomatic synapses Axonal endings ? cell body of neuron Presynaptic neuron Conducts impulses toward the synapse Postsynaptic neuron Transmits impulse away from the synapse

66. SYNAPSE TYPES Electrical Synapses Less common than chemical synapses Correspond to gap junctions found elsewhere Cytoplasm of adjacent neurons connected through protein channels Ions flow directly between neurons Neurons are “electrically coupled” Transmission across synapse is very rapid

67. SYNAPSE TYPES Chemical Synapses Specialized for release & reception of neurotransmitters Two parts Axonal terminal of presynaptic neuron Contains numerous synaptic vesicles filled with neurotransmitter molecules Neurotransmitter receptor region Present on dendrite or cell body of postsynaptic neuron Separated by synaptic cleft Remember this stuff in muscles?

68. SYNAPSE Nerve impulse reaches axonal terminal Voltage-gated Ca2+ channels open in axon Ca2+ enters presynaptic neuron Neurotransmitter is released via exocytosis Vesicles fuse with axonal membrane Neurotransmitter binds to postsynaptic receptors Ion channels open in postsynaptic membrane Result is excitation or inhibition

69. SYNAPSE Binding of neurotransmitter to its receptor is reversible Permeability affected as long as neurotransmitter is bound to its receptor Neurotransmitters do not persist in the synaptic cleft Degraded by enzymes associated with postsynaptic membrane Reuptake by astrocytes or presynaptic terminal Diffusion of neurotransmitters away from synapse

70. SYNAPSE Transmission of impulses along axon can be very fast Up to 300 mph (150 m/s) Transmission of a signal across a synapse is slow in comparison Leads to “synaptic delay” ~0.3 0 5.0 milliseconds Rate-limiting step of neural transmission Transmission along multisynaptic pathways is slower than along pathways with fewer synapses

71. SYNAPSE Postsynaptic Potentials Many receptors present on postsynaptic membranes open ion channels Ligand-gated channels Electrical signal converted to chemical signal converted to electrical signal Graded potential is produced Magnitude is dependent upon amount of neurotransmitter released Action potential may be produced Either excitatory or inhibitory

72. SYNAPSE Excitatory Synapses Neurotransmitter binding causes depolarization Single type of channel opens in membrane Na+ and K+ simultaneously diffuse through the membrane in opposite directions Na+ influx exceeds K+ efflux Net depolarization occurs Local graded depolarization events formed “Excitatory postsynaptic potential (EPSP)” May trigger an action potential at axon hillock Voltage-gated channels at hillock open, etc.

73. SYNAPSE Inhibitory Synapses Neurotransmitter binding reduces a postsynaptic neuron’s ability to generate an action potential Increased permeability to K+ and Cl-, not Na+ Postsynaptic neuron becomes less likely to fire “Inhibitory postsynaptic potential (IPSP)”

74. SYNAPSE Summation A single ESPS cannot induce an action potential Requires multiple axonal termini firing in concert Hundreds or thousands of EPSPs act together “Summation” Two types of summation Temporal summation One or more neurons transmit in rapid succession Spatial summation Simultaneous stimulation by numerous termini from one or more neurons (Both EPSPs and IPSPs summate)

75. SYNAPSE Synaptic Potentiation Repeated or continuous use of a synapse enhances presynaptic neuron’s ability to excite Larger postsynaptic potentials produced “Synaptic potentiation” Greater [Ca++] inside presynaptic terminals More neurotransmitter released Larger EPSPs produced

76. SYNAPSE Presynaptic Inhibition Release of excitatory neurotransmitter can be inhibited by activity of another neuron Less neurotransmitter released and bound

77. SYNAPSE Neuromodulation Presynaptic event effecting postsynaptic activity Can occur when neurotransmitter acts via slow changes in target cell metabolism Can occur when chemicals other than neurotransmitters modify neuronal activity Neuromodulators can influence Synthesis, release, degradation, or reuptake of neurotransmitters Sensitivity of postsynaptic membrane

78. NEUROTRANSMITTERS Facilitate communication by neurons Neurotransmitter release or destruction can be enhanced or inhibited How can synaptic transmission be affected? Enhanced or inhibited neurotransmitter release Enhanced or inhibited neurotransmitter degradation Blocked receptors or postsynaptic membrane

79. NEUROTRANSMITTERS More than fifty neurotransmitters identified Most neurons make two or more Can be released singly or together Classification by Structure Acetylcholine (ACh) Biogenic amines Amino acids Peptides ATP Dissolved gases Classification by Function Excitatory/Inhibitory Direct/Indirect

80. NEUROTRANSMITTERS Two main types of neurotransmitter receptors Channel-linked receptors Mediate fast synaptic transmission G protein-linked receptors Mediate slow synaptic responses

81. RECEPTORS Channel-Linked Receptors “Ligand-gated ion channels” Composed of “rosettes” of several protein subunits surrounding central pore Ligand binds to subunit(s) ? subunit shape changes ? central channel opened

82. RECEPTORS G Protein-Linked Receptors Indirect, slow, and prolonged response Neurotransmitter binding activates G protein Intracellular enzymatic activity activated Second messenger(s) formed inside the cell Cellular response

83. NEURAL INTEGRATION Neurons function in groups, not singly These various components must interact Multiple levels of neural integration

84. NEURONAL POOLS Neurons in CNS are organized into pools Functional groups Integrate incoming information Forward processed information

85. NEURONAL POOLS Simple Neuronal Pool Incoming fiber branches profusely upon entering pool EPSPs induced in multiple postsynaptic neurons EPSPs exceed threshold in some neurons Mainly those with multiple synaptic contacts EPSPs do not exceed threshold in some neurons Mainly those with fewer synaptic contacts Some close to threshold “Facilitated zone”

86. TYPES OF CIRCUITS Patterns of synaptic connections in neuronal pools are called circuits Determine neuronal pool’s functional capabilities Four basic circuit patterns Diverging circuits Converging circuits Reverberating (oscillating) circuits Parallel after-discharge circuits

87. TYPES OF CIRCUITS Diverging (Amplifying) Circuit One incoming fiber triggers responses in ever-increasing numbers of neurons Common in both sensory and motor systems

88. TYPES OF CIRCUITS Converging Circuits Pool receives inputs from several neurons Circuit has “funneling” effect Common in sensory and motor systems

89. TYPES OF CIRCUITS Reverberating (Oscillating) Circuits Incoming signal travels through chain of neurons Each neuron makes synapses with neurons upstream in the pathway Involved in rhythmic activities (e.g., breathing)

90. TYPES OF CIRCUITS Parallel After-Discharge Circuits Incoming fiber stimulated parallel neuron arrays Parallel arrays ultimately stimulate a common output cell Create prolonged burst of impulses Involved in complex mental processing

91. PROCESSING PATTERNS Serial input processing Input travels along one pathway to a specific destination All-or-nothing function of system e.g., reflexes Parallel input processing Inputs are segregated into multiple pathways Integrated in different CNS regions Different circuits do different things with input Not repetitious