Nervous Tissue and Function Function of the

Nervous Tissue and Function § Function of the Nervous System § Organization (Structural and Functional) § Supporting Cells of the Nervous System § Anatomy of a Neuron § Classification of Neurons by Function § Graded and Action Potentials § Myleination and MS § Reflexes § Synapses § EPSPs and IPSPs § Neurotransmitters

Functional Classification of the Peripheral Nervous System

Organization of the Nervous System and reflexes inhibitory stimulatory

Peripheral nervous system (PNS) Central nervous system (CNS) Cranial nerves and spinal nerves Communication lines between the CNS and the rest of the body Brain and spinal cord Integrative and control centers Sensory (afferent) division Somatic and visceral sensory nerve fibers Conducts impulses from receptors to the CNS Somatic sensory fiber Motor (efferent) division Motor nerve fibers Conducts impulses from the CNS to effectors (muscles and glands) Somatic nervous system Somatic motor (voluntary) Conducts impulses from the CNS to skeletal muscles Skin Visceral sensory fiber Stomach Skeletal muscle Motor fiber of somatic nervous system Sympathetic division Mobilizes body systems during activity Sympathetic motor fiber of ANS Structure Function Sensory (afferent) division of PNS Motor (efferent) division of PNS Parasympathetic motor fiber of ANS Autonomic nervous system (ANS) Visceral motor (involuntary) Conducts impulses from the CNS to cardiac muscles, smooth muscles, and glands Parasympathetic division Conserves energy Promotes housekeeping functions during rest Heart Bladder Figure 11. 2

Nervous Tissue and Function § Function of the Nervous System § Organization (Structural and Functional) § Supporting Cells of the Nervous System § Anatomy of a Neuron § Classification of Neurons § Neuron Function Graded and Action Potentials § Myleination and MS § Reflexes § Synapses § EPSPs and IPSPs § Neurotransmitters

Nervous Tissue: Support Cells (Neuroglia) § Astrocytes • Abundant, star-shaped cells • Brace neurons • Form barrier between capillaries and neurons • Control the chemical environment of the brain • Help transfer nutrients between capillaries and neurons • Mop up and recapture potassium ions and neurotransmitters "Star cells connect and protect"

Nervous Tissue: Support Cells § Microglia • Spider-like phagocytes • Dispose of debris by phagocytosis • Monitor neuron health "Tiny garbage spiders"

Ependymal Cells (literally, “wrapping garment” cells) • Range in shape from squamous to columnar • May be ciliated • Line the central cavities of the brain and spinal column • Separate the CNS interstitial fluid from the cerebrospinal fluid in the cavities Fluid-filled cavity Ependymal cells Brain or spinal cord tissue

Nervous Tissue: Support Cells § Oligodendrocytes • Produce myelin sheath around nerve fibers in the central nervous system "Oligos insulate"

Nervous Tissue: Support Cells § Schwann cells • Form myelin sheath in the peripheral nervous system • Satellite cells • Surround neuron cell bodies in the PNS Satellite cells Cell body of neuron Schwann cells (forming myelin sheath) Nerve fiber

Nervous Tissue and Function § Function of the Nervous System § Organization (Structural and Functional) § Supporting Cells of the Nervous System § Anatomy of a Neuron § Classification of Neurons § Neuron Function Graded and Action Potentials § Myleination and MS § Reflexes § Synapses § EPSPs and IPSPs § Neurotransmitters

Dendrites (receptive regions) Cell body (biosynthetic center and receptive region) Nucleolus Axon (impulse generating and conducting region) Nucleus Nissl bodies Impulse direction Node of Ranvier (Rough ER) Axon hillock (b) Schwann cell Neurilemma (one inter. Terminal node) branches Axon terminals (secretory region) Figure 11. 4 b

Neuron Cell Body Names and Locations Clusters of cell bodies Bundles of nerve fibers (neuronal processes) CNS Nuclei Tracts § White matter -dense myelinated fibers § Gray matter- unmyelinated fibers and cell bodies PNS Ganglia Nerves (bundles of axons)

Axons and Connection(s) to Other Neurons Synapse

Nerve Fiber Coverings § In the PNS, Schwann cells produce myelin sheaths in jelly-roll like fashion § Nodes of Ranvier – gaps in myelin sheath along the axon § In the CNS, oligodendrocytes produce myelin sheaths and have no neurilemma (so cannot regenerate if damaged). § In multiple sclerosis (MS) the myelin sheaths are destroyed (autoimmunity) leading to poorly functioning muscles

Nervous Tissue and Function § Function of the Nervous System § Organization (Structural and Functional) § Supporting Cells of the Nervous System § Anatomy of a Neuron § Classification of Neurons by Function § Graded and Action Potentials § Myleination and MS § Reflexes § Synapses § EPSPs and IPSPs § Neurotransmitters

Functional Classification of Neurons § Sensory (afferent) neurons • Carry impulses from the sensory receptors • Cell bodies outside the CNS o Cutaneous sense organs o Proprioceptors – detect stretch or tension § Motor (efferent) neurons • Carry impulses from the central nervous system • Cell bodies inside the CNS § Interneurons (association neurons) • Found in neural pathways in the central nervous system • Connect sensory and motor neurons • Cell bodies inside the CNS From skin receptors, muscles and tendons

Nervous Tissue and Function § Function of the Nervous System § Organization (Structural and Functional) § Supporting Cells of the Nervous System § Anatomy of a Neuron § Classification of Neurons by Function § Graded and Action Potentials § Myleination and MS § Reflexes § Synapses § EPSPs and IPSPs § Neuraltransmitters

Principles of Electricity § Opposite charges attract each other § Energy is required to separate opposite charges across a membrane § Energy is liberated when the charges move toward one another § If opposite charges are separated, the system has potential energy

Definitions § Voltage (V): measure of potential energy generated by separated charges § Potential difference: the voltage or difference in charge measured between two points § Current (I): the flow of electrical charge (ions) between two points § Resistance (R): hindrance to charge flow (provided by the plasma membrane) § Insulator: substance with high electrical resistance § Conductor: substance with low electrical resistance § Intracellular fluid (ICF) - cytoplasm of neuron § Extracellular fluid (ECF) - fluid outside a neuron cell

Role of Membrane Ion Channels (Protein “Gates”) § Two main types of ion channels: 1. Leakage (nongated) channels — always open 2. Receptor Gated channels (three types): Ø Ø Ø Neurotransmitter chemical attached to receptor Na+ Chemical binds Chemically gated (ligandgated) channels—open with binding of a specific neurotransmitter Closed Voltage-gated channels — open and close in response to changes in membrane potential Na+ K+ K+ Membrane voltage changes Open Na+ Mechanically gated channels —open and close in response to physical deformation of receptors Closed Open

Potential difference across the membrane of a resting cell (= Resting Potential) Voltmeter Plasma membrane Microelectrode inside cell Intracellular fluid (ICF) Extracellular fluid (ECF) Ground electrode outside cell Electrochemical gradient or potential difference is established by the powered pumping of more positive ions in ECF than ICF. Axon Neuron Figure 11. 7

Resting Membrane Potential § Differences in ionic makeup + K+ Na+ Na+ + Na Cl– +Na + Na ECF Na+ Na+ Na+ Cl– Na+ • ICF has lower concentration of Na+ and Cl– than ECF • ICF has higher concentration of K+ and negatively charged proteins (A–) than ECF § Differential permeability of membrane ICF A- + K+ K+ K+ A- • Impermeable to A– A- Cl– Na+ ECF K+ ICF • Slightly permeable to Na+ (through leakage channels) A- K+ Cl– • 75 times more permeable to K+ (more leakage channels) • Freely permeable to Cl– § Negative interior of the cell is due to much greater diffusion of K+ out of the cell than Na+ diffusion into the cell § Sodium-potassium pump stabilizes the resting membrane potential by maintaining the concentration gradients for Na+ and K+ ECF ICF ++ + + + K+

To Recap…. The concentrations of Na+ and K+ on each side of the membrane are different. The Na+ concentration is higher outside the cell. The K+ concentration is higher inside the cell. Outside cell K+ (5 m. M ) Na+ (140 m. M ) K+ (140 m. M ) Na+ (15 m. M ) Inside cell The permeabilities of Na+ and K+ across the membrane are different. Suppose a cell has only K+ channels. . . K+ loss through abundant leakage channels establishes a negative membrane potential. K+ leakage channels K+ K+ K+ Na+ K+ K+ Na+-K+ ATPases (pumps) maintain the concentration gradients of Na+ and K+ across the membrane. Cell interior – 90 m. V Now, let’s add some Na+ channels to our cell. . . Na+ entry through leakage channels reduces the negative membrane potential slightly. Cell interior – 70 m. V Na+-K+ pump Finally, let’s add a pump to compensate for leaking ions. Na+-K+ ATPases (pumps) maintain the concentration gradients, resulting in the resting membrane potential. Cell interior – 70 m. V Figure 11. 8

Membrane Potentials That Act as Signals § Membrane potential changes when: • Concentrations of ions across the membrane change • Permeability of membrane to ions changes § Changes in membrane potential are signals used to receive, integrate and send information

Membrane Potentials That Act as Signals § Two types of signals • Graded potentials o Incoming short-distance signals o Short-lived, localized changes in membrane potential o Depolarizations or hyperpolarizations o Graded potential spreads as local currents change the membrane potential of adjacent regions o Act to enhance or limit chances of an action potential but does not send an electrical “message” • Action potentials o Long-distance signals of axons

Graded Potential: Depolarization Depolarizing stimulus Inside positive Inside negative Depolarization Resting potential § Stimulus causes gated ion channels to open • E. g. , receptor potentials, generator potentials, postsynaptic potentials § Magnitude varies directly (graded) with stimulus strength § Decrease in magnitude with distance as ions flow and diffuse through leakage channels Time (ms) (a) Depolarization: The membrane potential moves toward 0 m. V, the inside becoming less negative (more positive). Increases the probability of producing a nerve impulse. Figure 11. 9 a

Graded Potential: Hyperpolarization Hyperpolarizing stimulus Resting potential Hyperpolarization Time (ms) (b) Hyperpolarization: The membrane potential increases, the inside becoming more negative. Decreases the probability of producing a nerve impulse. Figure 11. 9 b

Membrane potential (m. V) Active area (site of initial depolarization) – 70 Resting potential Distance (a few mm) (c) Decay of membrane potential with distance: Because current is lost through the “leaky” plasma membrane, the voltage declines with distance from the stimulus (the voltage is decremental ). Consequently, graded potentials are short-distance signals. Figure 11. 10 c

Membrane Potentials That Act as Signals § Two types of signals • Graded potentials o Incoming short-distance signals o Short-lived, localized changes in membrane potential o Depolarizations or hyperpolarizations o Graded potential spreads as local currents change the membrane potential of adjacent regions • Action potentials o Long-distance signals of axons

Action Potential (AP) § Brief reversal of membrane potential with a total amplitude of ~100 m. V § Occurs in muscle cells and axons of neurons § Does not decrease in magnitude over distance § Principal means of long-distance neural communication

Anatomy of an Action Potential • Na+ channel slow inactivation gates close • Only leakage channels for Na+ and K+ are open §Depolarizing local currents open voltagegated Na+ channels • Membrane permeability to Na+ declines to resting levels • All gated Na+ and K+ channels are closed §Na+ influx causes more depolarization • K+ exits the cell and internal negativity is restored 3 Repolarization 2 Depolarization 3 3 2 2 Action potential Na+ permeability Action potential K+ permeability Threshold 1 1 44 Time (ms) 1 Relative membrane permeability Membrane potential (m. V) 1 Resting state • Slow voltage-sensitive K+ gates open • Some K+ channels remain open, allowing excessive K+ efflux • This causes afterhyperpolarization of the membrane (undershoot) 4 Hyperpolarization Channel gating (online animation) Figure 11. 11 (1 of 5)

Voltage Change at Point in Neuron as Action Potential Passes By Voltage at 0 ms Recording electrode (a) Time = 0 ms. Action potential has not yet reached the recording electrode. Resting potential Peak of action potential Hyperpolarization Figure 11. 12 a

Voltage Change at Point in Neuron as Action Potential Passes By Voltage at 2 ms (b) Time = 2 ms. Action potential peak is at the recording electrode. Figure 11. 12 b

Voltage Change at Point in Neuron as Action Potential Passes By Voltage at 4 ms Action potential online Figure 11. 12 c (c) Time = 4 ms. Action potential peak is past the recording electrode. Membrane at the recording electrode is still hyperpolarized.

Threshold Stimulus § Subthreshold stimulus—weak local depolarization that does not reach threshold § Threshold stimulus—strong enough to push the membrane potential toward and beyond threshold (Membrane is depolarized by 15 to 20 m. V) § AP is an all-or-none phenomenon—action potentials either happen completely, or not at all § All action potentials are alike and are independent of stimulus intensity

Action potentials Threshold Stimulus Time (ms) Figure 11. 13

Refractory Periods Absolute refractory period Depolarization (Na+ enters) Relative refractory period ARP §Time from the opening of the Na+ channels until the resetting of the channels §Ensures that each AP is an all-or-none event §Enforces one-way transmission of nerve impulses RRP • Most Na+ channels have returned to their resting state • Some K+ channels are still open • Repolarization is occurring §Threshold for AP generation is elevated §Exceptionally strong stimulus may generate an AP Repolarization(K+ leaves) After-hyperpolarization Stimulus Time (ms) Figure 11. 14

AP Velocity a Function of Axon Diameter and Myelination Stimulus Size of voltage (a) In a bare plasma membrane (without voltage-gated channels), as on a dendrite, voltage decays because current leaks across the membrane. Voltage-gated Stimulus ion channel (b) In an unmyelinated axon, voltage-gated Na+ and K+ channels regenerate the action potential at each point along the axon, so voltage does not decay. Conduction is slow because movements of ions and of the gates of channel proteins take time and must occur before voltage regeneration occurs. Stimulus Myelin sheath (c) In a myelinated axon, myelin keeps current in axons (voltage doesn’t decay much). APs are generated only in the nodes of Ranvier and appear to jump rapidly from node to node, about 30 times faster than a bare axon. Continuous conduction Node of Ranvier 1 mm Saltatory conduction Myelin sheath Figure 11. 15

Multiple Sclerosis (MS) § Nature • An autoimmune disease that mainly affects young adults • Symptoms: visual disturbances, weakness, loss of muscular control, speech disturbances, and urinary incontinence • Myelin sheaths in the CNS become nonfunctional scleroses • Shunting and short-circuiting of nerve impulses occurs • Impulse conduction slows and eventually ceases § Treatment • Some immune system–modifying drugs, including interferons and Copazone: o Hold symptoms at bay o Reduce complications o Reduce disability

Nervous Tissue and Function § Function of the Nervous System § Organization (Structural and Functional) § Supporting Cells of the Nervous System § Anatomy of a Neuron § Classification of Neurons by Function § Graded and Action Potentials § Myleination and MS § Reflexes § Synapses § EPSPs and IPSPs § Neurotransmitters

The Reflex Arc

Types of Reflexes and Regulation § Autonomic reflexes • Smooth muscle regulation • Heart and blood pressure regulation • Regulation of glands • Digestive system regulation § Somatic reflexes • Activation of skeletal muscles

Nervous Tissue and Function § Function of the Nervous System § Organization (Structural and Functional) § Supporting Cells of the Nervous System § Anatomy of a Neuron § Classification of Neurons by Function § Graded and Action Potentials § Myleination and MS § Reflexes § Synapses § EPSPs and IPSPs § Neurotransmitters

Two Kinds of Synapses § Chemical Synapses • Specialized for the release and reception of neurotransmitters • Typically composed of two parts o Axon terminal of the presynaptic neuron, which contains synaptic vesicles o Receptor region on the postsynaptic neuron § Electrical Synapses • Less common than chemical synapses • Neurons are electrically coupled (joined by gap junctions) • Communication is very rapid, and may be unidirectional or bidirectional • Are important in: o Embryonic nervous tissue o Some brain regions

How Neurons Communicate at Synapses Events at the Synapse (online animation) Narrated synapse (online) § Irritability – ability to respond to stimuli § Conductivity – ability to transmit an impulse` Sodium. Potassium pump (online animation)

Chemical synapses transmit signals from one neuron to another using neurotransmitters. Presynaptic neuron Postsynaptic neuron 1 Action potential arrives at axon terminal. Mitochondrion Ca 2+ Axon terminal Ca 2+ Synaptic cleft Synaptic vesicles Postsynaptic neuron Figure 11. 17, step 1

Chemical synapses transmit signals from one neuron to another using neurotransmitters. Presynaptic neuron Postsynaptic neuron 1 Action potential arrives at axon terminal. 2 Voltage-gated Ca 2+ channels open and Ca 2+ enters the axon terminal. Mitochondrion Ca 2+ Axon terminal Ca 2+ Synaptic cleft Synaptic vesicles Postsynaptic neuron Figure 11. 17, step 2

Chemical synapses transmit signals from one neuron to another using neurotransmitters. Presynaptic neuron Postsynaptic neuron 1 Action potential arrives at axon terminal. 2 Voltage-gated Ca 2+ channels open and Ca 2+ enters the axon terminal. Mitochondrion Ca 2+ 3 Ca 2+ entry causes neurotransmittercontaining synaptic vesicles to release their contents by exocytosis. Axon terminal Ca 2+ Synaptic cleft Synaptic vesicles Postsynaptic neuron Figure 11. 17, step 3

Chemical synapses transmit signals from one neuron to another using neurotransmitters. Presynaptic neuron Postsynaptic neuron 1 Action potential arrives at axon terminal. 2 Voltage-gated Ca 2+ channels open and Ca 2+ enters the axon terminal. Mitochondrion Ca 2+ 3 Ca 2+ entry causes neurotransmittercontaining synaptic vesicles to release their contents by exocytosis. 4 Neurotransmitter diffuses across the synaptic cleft and binds to specific receptors on the postsynaptic membrane. Axon terminal Ca 2+ Synaptic cleft Synaptic vesicles Postsynaptic neuron Figure 11. 17, step 4

Ion movement Graded potential 5 Binding of neurotransmitter opens ion channels, resulting in graded potentials. Figure 11. 17, step 5

Enzymatic degradation Reuptake Diffusion away from synapse 6 Neurotransmitter effects are terminated by reuptake through transport proteins, enzymatic degradation, or diffusion away from the synapse. Figure 11. 17, step 6

Chemical synapses transmit signals from one neuron to another using neurotransmitters. Presynaptic neuron Postsynaptic neuron 1 Action potential arrives at axon terminal. 2 Voltage-gated Ca 2+ channels open and Ca 2+ enters the axon terminal. Mitochondrion Ca 2+ 3 Ca 2+ entry causes neurotransmittercontaining synaptic vesicles to release their contents by exocytosis. Axon terminal Ca 2+ Synaptic cleft Synaptic vesicles 4 Neurotransmitter diffuses across the synaptic cleft and binds to specific receptors on the postsynaptic membrane. Postsynaptic neuron Ion movement Enzymatic degradation Graded potential Reuptake Diffusion away from synapse 5 Binding of neurotransmitter opens ion channels, resulting in graded potentials. Events at the Synapse (online animation) Narrated synapse (online) 6 Neurotransmitter effects are terminated by reuptake through transport proteins, enzymatic degradation, or diffusion away from the synapse. Sodium. Potassium pump (online animation) Figure 11. 17

Nervous Tissue and Function § Function of the Nervous System § Organization (Structural and Functional) § Supporting Cells of the Nervous System § Anatomy of a Neuron § Classification of Neurons by Function § Graded and Action Potentials § Myleination and MS § Reflexes § Synapses § EPSPs and IPSPs § Neurotransmitters

Excitatory Synapses and EPSPs Neurotransmitter binds to and opens chemically gated channels that allow simultaneous flow of Na + and K+ in opposite directions § Na+ influx is greater that K+ efflux, causing a net depolarization § Excitatory postsynaptic potential (EPSP) helps trigger AP at axon hillock if EPSP is of threshold strength and opens the voltage-gated channels Membrane potential (m. V) § Threshold An EPSP is a local depolarization of the postsynaptic membrane that brings the neuron closer to AP threshold. Neurotransmitter binding opens chemically gated ion channels, allowing the simultaneous passage of Na+ and K+. Stimulus Time (ms) Figure 11. 18 a

Inhibitory Synapses and Inhibitory Postsynaptic Potential (IPSPs ) Neurotransmitter binds to and opens channels for K+ or Cl– § Causes a hyperpolarization (the inner surface of membrane becomes more negative) § Reduces the postsynaptic neuron’s ability to produce an action potential Membrane potential (m. V) § Threshold An IPSP is a local hyperpolarization of the postsynaptic membrane and drives the neuron away from AP threshold. Neurotransmitter binding opens K+ or Cl– channels. Stimulus Time (ms) Figure 11. 18 b

Nervous Tissue and Function § Function of the Nervous System § Organization (Structural and Functional) § Supporting Cells of the Nervous System § Anatomy of a Neuron § Classification of Neurons by Function § Graded and Action Potentials § Myleination and MS § Reflexes § Synapses § EPSPs and IPSPs § Neurotransmitters

Chemical Classes of Neurotransmitters § Acetylcholine (Ach) (Mostly excitory in CNS, PNS if prolonged prod. tetanus (with nerve gases), receoptors destroyed in myasthenia gravis) • Released at neuromuscular junctions and some ANS neurons • Synthesized by enzyme choline acetyltransferase • Degraded by the enzyme acetylcholinesterase (ACh. E) § Biogenic amines o Catecholamines Ø Dopamine (“Feeling good” CNS neurotransmitter, uptake blocked by cocaine, excitory or inhibitory), norepinephrine (NE), and epinephrine o Indolamines Ø Serotonin (Roles in sleep, appetite, nausea, mood; blocked by seritonin-specific reuptake inhibitors (SSRIs) like Prozac and LSD, enhanced by ecstasy (3, 4 -Methylenedioxymethamphetamine)), histamine • Broadly distributed in the brain; play roles in emotional behaviors and the biological clock § Amino acids include: o GABA—Gamma ( )-aminobutyric acid (inhibitory brain NT augmented by alcohol, benzodiazepine-valium) o Glutamate (excitory in CNS, causes stroke when overreleased, overstimulation of neurons) , Glycine, Aspartate § Peptides (neuropeptides) include: o Substance P, endorphins, somatostatin, cholecystokinin § Purines such as ATP § Gases and lipids • NO, CO, Endocannabinoids