Chapter 11: Fundamentals of the Nervous System and Nervous Tissue

Nervous System Master controlling and communicating system of the body Cells communicate by electrical signals and chemical signals Rapid and specific Usually cause an immediate response Neurons = nerve cells

Functions 3 overlapping functions 1. Sensory input NS uses its millions of sensory receptors to monitor changes Sensory input 2. Integration NS process and interprets sensory input and decides what should be done integration 3. Motor Output response by activating effector organs muscles and glands

Figure 11.1 Sensory input Motor output Integration

Divisions Central NS brain and spinal cord Dorsal body cavity Integrating and command center of NS Interprets sensory input and dictates motor responses based on reflexes current and past experience

Divisions Peripheral NS Part of NS outside the CNS Consists of nerves bundles of axons extend brain and spinal cord Spinal nerves carry impulses to and from the brain Cranial nerves impulses to and from the brain

Divisions of PNS 2 Functions Sensory, or afferent, division carrying towards Nerve fibers (axons) and convey impulses to CNS Somatic afferent fibers transmit impulses from skeletal muscle Visceral afferent fibers transmit impulses from visceral organs

Divisions of PNS Motor, or efferent, division carrying away Impulses from CNS to effector organs Activate muscles to contract and glands to secrete Effect response 1.Somatic NS somatic motor nerve fibers conduct impulses from CNS to skeletal muscle -voluntary NS 2.Automatic NS (ANS) visceral motor nerve fibers -Regulate activity of smooth muscle, cardiac muscle and glands -a law unto itself -Cannot control pumping of heart or food through digestive tract -2 functional subdivisions sympathetic and parasympathetic NS work in opposition to each other

Figure 11.2 Central nervous system (CNS) Brain and spinal cord Integrative and control centers Peripheral nervous system (PNS) Cranial nerves and spinal nerves Communication lines between the CNS and the rest of the body Parasympathetic division Conserves energy Promotes house- keeping functions during rest Motor (efferent) division Motor nerve fibers Conducts impulses from the CNS to effectors (muscles and glands) Sensory (afferent) division Somatic and visceral sensory nerve fibers Conducts impulses from receptors to the CNS Somatic nervous system Somatic motor (voluntary) Conducts impulses from the CNS to skeletal muscles Sympathetic division Mobilizes body systems during activity Autonomic nervous system (ANS) Visceral motor (involuntary) Conducts impulses from the CNS to cardiac muscles, smooth muscles, and glands Structure Function Sensory (afferent) division of PNS Motor (efferent) division of PNS Somatic sensory fiber Visceral sensory fiber Motor fiber of somatic nervous system Skin Stomach Skeletal muscle Heart Bladder Parasympathetic motor fiber of ANS Sympathetic motor fiber of ANS

Histology of Nervous Tissue Highly cellular Less than 20 % of CNS extracellular space Densely packed and tightly intertwined 2 principal cells 1. Supporting cells neuroglia Small cells that surround and wrap neurons 2. Neurons excitable nerve cells that transmit signals

Neuroglia nerve glue Glial cells 6 types each own unique function Supportive scaffold for neurons Produce chemicals that guide young neurons growth Wrap around and insulate neuronal process to speed up action potential conduction

Neuroglia in CNS Astrocytes Microglia Ependymal cells Oligoderocytes Most have branching processes (extensions) and a central cell body Distinguished by smaller size and darker staining nucleus

CNS Neuroglia - Astrocytes star cells Most abundant and most versatile Radiating processes cling to neurons and synaptic endings Cover nearby capillaries Support and branch neurons Anchor them to nutrient supply Role in making exchanges capillaries neurons mopping up leaked K ions and recapturing released neurotransmitters Connected by gap junctions Signal each other with Ca

Figure 11.3a (a) Astrocytes are the most abundant CNS neuroglia. Capillary Neuron Astrocyte

CNS Neuroglia - Microglia Small oviod cell with long thorny processes Processes touch neurons monitor health When neurons injuries or in trouble migrate towards them Transform into macrophages phagocytize foreign debris Protective role

Figure 11.3b (b) Microglial cells are defensive cells in the CNS. Neuron Microglial cell

CNS Neuroglia Epedymal Cells wrapping garment Shape squamous columnar Many ciliated Line central cavities of brain and spinal cord Permeable barrier between cerebral spinal fluid and tissue fluid of CNS Cilia circulated fluid

Figure 11.3c Brain or spinal cord tissue Ependymal cells Fluid-filled cavity (c) Ependymal cells line cerebrospinal fluid-filled cavities.

CNS Neuroglia Oligodendrocytes Fewer processes Line up along thicker neuron fibers and wrap processes around them Covering sheaths myelin sheaths

Figure 11.3d (d) Oligodendrocytes have processes that form myelin sheaths around CNS nerve fibers. Nerve fibers Myelin sheath Process of oligodendrocyte

Neuroglia in PNS 1. Satellite Cells surround neuron cell bodies located in PNS Thought to have same functions as astrocytes 2. Schwann Cells surrond and form myelin sheaths in PNS Function similar to oligodendrocytes Vital to regeneration of damaged nerves

Figure 11.3d (d) Oligodendrocytes have processes that form myelin sheaths around CNS nerve fibers. Nerve fibers Myelin sheath Process of oligodendrocyte

Neurons Nerve cell Structural unit of NS Highly specialized cells Conduct messages nerve impulses Large complex cells Cell body and processes Plasma membrane electrical signaling Cell-cell interactions

Neurons Special characteristics 1. extreme longevity can function optimally over a lifetime ~100 years 2. amitotic loose ability to divide Cannot be replaced if destroyed Exceptions olfactory epithelium and hippocampel regions stem cells Cannot survive for more than a few minutes without oxygen 3. High metabolic rate require continuous and abundant oxygen and glucose

Figure 11.4b Dendrites (receptive regions) Cell body (biosynthetic center and receptive region) Nucleolus Nucleus Nissl bodies Axon (impulse generating and conducting region) Axon hillock Neurilemma Terminal branches Node of Ranvier Impulse direction Schwann cell (one inter- node) Axon terminals (secretory region) (b)

Neuron Cell Body Spherical nucleus surrounded by cytoplasm Perikaryon or soma cell body Ranges in diameter from 5 to 140 um Major biosynthetic center of the neuron Usual organelles Clustered and free ribosomes and rough ER most active and developed in the body Rough ER Nissl bodies chromatophilic substance Golgi well developed and form arci or complete circle around nucleus Mitochondria - scattered

Figure 11.4b Dendrites (receptive regions) Cell body (biosynthetic center and receptive region) Nucleolus Nucleus Nissl bodies Axon (impulse generating and conducting region) Axon hillock Neurilemma Terminal branches Node of Ranvier Impulse direction Schwann cell (one inter- node) Axon terminals (secretory region) (b)

Neuron Cell Body Neurofibrils bundles of intermediate filaments Maintain cell shape and integrity Pigment inclusions black melanin, red iron containing pigment, gold brown pigment Lipofuscin ageing pigment accumulates in neurons of elderly Most cell bodies in CNS are protected by bones of skull and vertebral column Clusters of cell bodies in CNS nuclei Clusters of cell bodies in PNS - ganglia

Neurons - Processes Arm like Extend from cell bodies Bundles of processes Tracts in CNS Nerves in PNS

Neurons - Processes 2 types 1. dendrites - short, tapering diffusely branching extensions Main receptive or input regions SA for receiving signals Convey incoming messages toward cell body Usually not AP but short distance signals called graded potentials

Neurons - Processes 2. Axon single Arises from axon hillock then narrows to form slender processes Some short or absent others long up to 3 to 4 ft Long axon = nerve fiber Axon branches axon collaterals Branches profusely at its end 10000 or more terminal branches telodendria Knob like distal ends axon terminals, synaptic knobs, boutons

Neurons - Processes Axon Cont Axon conducting region Generates nerve impulses and transmits them away from cell body along plasma membrane axolemma Nerve impulses from axon hillock to axon to axon terminal secretory region Depends on 1. cell body to renew necessary proteins and membrane components 2. efficient transport mechanisms to distribute

Neurons - Processes Axon cont Anterograde movement movement toward an axon terminal Retrograde movement movement in the opposite direction Viruses and bacteria toxins damage neural tissues use retrograde axonal transport to reach cell body polio, rabies, herpes, tetanus

Neurons Myelin Sheath and Neurilemma Myelin Sheath whitish, fatty (protein-lipid) Protects and insulates fibers Increases the speed of transmission of nerve impulses Myelintaed fibers conduct fast Unmyelinated fibers slower Dendrites always unmyelinated Formed by Schwann cells indent to receive an axon, then wrap around them

Figure 11.5a (a) Myelination of a nerve fiber (axon) Schwann cell cytoplasm Axon Neurilemma Myelin sheath Schwann cell nucleus Schwann cell plasma membrane 1 2 3 A Schwann cell envelopes an axon. The Schwann cell then rotates around the axon, wrapping its plasma membrane loosely around it in successive layers. The Schwann cell cytoplasm is forced from between the membranes. The tight membrane wrappings surrounding the axon form the myelin sheath.

Neurons Myelin Sheath and Neurilemma Neurilemma exposed part of plasma membrane Gaps in sheaths nodes of Ranvier myelin sheath gaps occur at regular intervals ~1 mm apart along axon Regions of brain and spinal cord White matter dense collections of myelinated fibers Gray matter nerve cell bodies and unmyelinated fibers

Classification of Neurons Structural grouped according to number of processes extending from cell body 3 major groups multipolar, bipolar, and unipolar

Structural Classification 1. Multipolar 3 or more processes 1 axon and the rest dendrites Most common 99 % of neurons Major type in CNS

Structural Classification 2. Bipolar Neurons 2 processes Axon and dendrite Extend from opposite sides of the cell Rare found in special sense organs Neurons in retina of eye olfactory mucosa

Structural Classification 3. Unipolar Neurons single short process Emerges and divides T-like proximal and distal Distal peripheral process Proximal central process Pseudounipolar neurons originate as bipolar fuse during development, chiefly in ganglia of PNS

Table 11.1 (1 of 3)

Table 11.1 (2 of 3)

Functional Classification Groups neurons according to direction in which nerve impulse travels relative to CNS 1. Sensory, or afferent, neurons transmit impulses from sensory receptors in skin or internal organs toward the CNS Almost always unipolar Cell bodies sensory ganglia outside CNS Distal parts - receptor sites Peripheral process very long Big tow 1 meter till spinal cord Receptive endings are naked

Functional Classification 2. Motor, or efferent, neurons carry impulses away from CNS to effector organs (muscles/glands) Multipolar Cell bodies located in CNS, except for some in ANS

Functional Classification 3. Interneurons, association neurons In between In neural pathways Shuttle signals through CNS where integration occurs Most confined in CNS 99 % of neurons in body Multipolar Diversity in size and fiber branching patterns

Table 11.1 (3 of 3)

Membrane Potentials Neurons highly irritable or excitable response to stimuli Stimulation impulse generated and conducted along length of axon Action Potential nerve impulse always the same regardless of source or type of stimulus

Membrane Potential Basic Principals Human body electrically neutral same number of + and Areas where 1 type of charge predominates regions that are + or Opposite charges attract energy must be used to separate them Coming together liberates energy

Membrane Potential Basic Principals Voltage measure of potential energy volts or mV Measured between 2 points Called potential difference or simply potential between 2 points Greater difference in charge higher voltage

Membrane Potential Basic Principals Current flow of electrical charge from one point to another Amount of charge depends on 2 factors voltage and resistance

Membrane Potential Basic Principals Resistance hindrance to charge flow provided by substances through which the current must pass High resistance insulators Low resistance - conductors

Membrane Potential Basic Principals Ohms Law Current is directly proportional to voltage Greater voltage (potential difference) the greater the current

Role of Membrane Ion Channels Membrane proteins ion channels Channels selective as to type of ion it allows to pass K+ ion channel only allow K+

Membrane Ion Channels Leakage, or nongated, channels open part of protein molecular gate changes shape to open and close to change channel in response to specific signals gated channels Chemically gated, or ligand gated, channels Opens when appropriate chemical binds Voltage gated channels open and close in response to changes in membrane potential Mechanically gated channels open in response to physical deformation of receptor

Figure 11.6 (b) Voltage-gated ion channels open and close in response to changes in membrane voltage. Na + ClosedOpen Receptor (a) Chemically (ligand) gated ion channels open when the appropriate neurotransmitter binds to the receptor, allowing (in this case) simultaneous movement of Na + and K +. Na + K+K+ K+K+ Neurotransmitter chemical attached to receptor Chemical binds ClosedOpen Membrane voltage changes

Membrane Ion Channels Ion gated channels open ions diffuse across membrane Creating electrical currents and voltage changes Voltage (V) = current (I) * resistance (R) Ions move along concentration gradients high low concentration Electrical gradients toward an area of opposite charge Together make electrochemical gradient

Resting Membrane Potential Potential difference measured with a voltmeter Membrane ~ 70 mV Negative on cytoplasmic side (inside) negative relative to outside Resting membrane potential Membrane said to be polarized Value varies -40mv -90 mV Generated by differences on ionic makeup

Figure 11.7 Voltmeter Microelectrode inside cell Plasma membrane Ground electrode outside cell Neuron Axon

Resting Membrane Potential Cytosol lower concentration of Na and higher concentration of K Na balanced by Cl K important role

Resting Membrane Potential Resting membrane impermeable to amniotic proteins Slightly permeable to Na 75X more permeable to K K ions diffuse out more easily than Na diffuses in Cell becomes negative inside Na K pump ejects 3 Na out and 2 k in Stabilizes membrane

Figure 11.8 Finally, lets add a pump to compensate for leaking ions. Na + -K + ATPases (pumps) maintain the concentration gradients, resulting in the resting membrane potential. Suppose a cell has only K + channels... K + loss through abundant leakage channels establishes a negative membrane potential. Now, lets add some Na + channels to our cell... Na + entry through leakage channels reduces the negative membrane potential slightly. The permeabilities of Na + and K + across the membrane are different. The concentrations of Na + and K + on each side of the membrane are different. Na + (140 mM ) K + (5 mM ) K + leakage channels Cell interior 90 mV Cell interior 70 mV Cell interior 70 mV K+K+ Na + Na+-K+ pump K+K+ K+K+ K+K+ K+K+ Na + K+K+ K+K+ K K+K+ K+K+ K+K+ K+K+ Outside cell Inside cell Na + -K + ATPases (pumps) maintain the concentration gradients of Na + and K + across the membrane. The Na + concentration is higher outside the cell. The K + concentration is higher inside the cell. K + (140 mM ) Na + (15 mM )

Membrane Potential - Signal Changes in membrane potential communication signal Can be produced by 1. anything that alters ion concentration on 2 sides of the membrane 2. anything that changes membrane permeability to any ion

Membrane Potential - Signal Changes in Potential 2 types of signals 1. Graded signals incoming signal operating over short distances 2. action potentials long distance signals

Membrane Potential - Changes Depolarization reduction in membrane potential Inside less negative than resting potential -70 to -65 mV Hyperpolarization membrane potential increases More negative that resting potential -70 to -75 mV

Figure 11.9a Depolarizing stimulus Time (ms) Inside positive Inside negative Resting potential Depolarization (a) Depolarization: The membrane potential moves toward 0 mV, the inside becoming less negative (more positive).

Figure 11.9b Hyperpolarizing stimulus Time (ms) Resting potential Hyper- polarization (b) Hyperpolarization: The membrane potential increases, the inside becoming more negative.

Graded Potentials Short lived, localized changes in membrane potential that can be either depolarizations or hyperpolarizations Changes cause current flows that decrease in magnitude with distance graded magnitude varies directly with stimulus strength Stronger stimulus more voltage changes and farther the flow

Graded Potential Triggered by a change in neurons environment causes gated ion channels to open sensory receptor excited heat, light, etc. resulting graded potential receptor potential or generator potential

Figure 11.10a Depolarized region Stimulus Plasma membrane (a) Depolarization: A small patch of the membrane (red area) has become depolarized.

Figure 11.10b (b) Spread of depolarization: The local currents (black arrows) that are created depolarize adjacent membrane areas and allow the wave of depolarization to spread.

Action Potential Brief reversal of membrane potential with a total amplitude (change in voltage) of about 100 mV (-70 mV to +30mV) Depolarization phase followed by a repolarization phase and often a short period of hyperpolarization Few milliseconds in duration Does not decrease in strength with distance

Action Potential Also called a nerve impulse Transmission identical in skeletal muscle cells and neurons Typically generated only in axons

Action potential 1 2 3 4 Resting state Depolarization Repolarization Hyperpolarization The big picture 11 2 3 4 Time (ms) Threshold Membrane potential (mV) Figure 11.11 (1 of 5)

Generation of an Action Potential 1. Resting State all gated Na and K channels are closed Only leakage channels are open, maintaining resting membrane potential Na 2 gates voltage sensitive activation gate and inactivation gate Depolarization opens and then inactivates the Na channels Both gates must be open for Na to enter K single voltage gate closed at resting and opens slowly

Generation of an Action Potential 2. Depolarization Phase Na Channels open Axon membrane depolarized by local currents, voltage gates Na channels open and Na rushes into cell Influx of Na positive charge opens more Na channels Depolarization at site reaches threshold Membrane potential becomes less and less negative and then overshoots to about +30 mV

Generation of an Action Potential 3. Repolarizing phase: Na channels are inactivating and K channels open Rising phase of the AP self limiting slow inactivation gates of Na channel begin to close Membrane permeability to N declines Voltage gated K channels open K rushes out of cell Initial negativity of resting neuron is restored - Repolarization

Generation of an Action Potential 4. Hyperpolarization some K channels remain open and Na channels reset Increased K permeability lasts longer than needed to restore resting state Excessive K permeability after hyperpolarization undershoot AP curve dips slightly Na channels begin to reset

Action potential Time (ms) 1 1 2 3 4 Na + permeability K + permeability The AP is caused by permeability changes in the plasma membrane Membrane potential (mV) Relative membrane permeability Figure 11.11 (2 of 5)

Propagation of an Action Potential AP transmitted along the axons entire length AP generated by an influx of Na Local currents that depolarizes adjacent membrane areas in forward directions (away from the origin of the nerve impulse) which opens voltage gated channels and triggers an AP Region where AP originated has just generated AP Na gates inactivated, so no AP generated there AP propagates away from the point of origin

Propagation of an Action Potential All or none phenomenon must reach threshold values if an axon is to fire Threshold membrane potential at which outward current created by K movement is exactly equal to the inward current created by Na movement Typically when membrane has been depolarized by 15 to 20 mV

Figure 11.12a 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 11.12b Voltage at 2 ms (b) Time = 2 ms. Action potential peak is at the recording electrode.

Figure 11.12c Voltage at 4 ms (c) Time = 4 ms. Action potential peak is past the recording electrode. Membrane at the recording electrode is still hyperpolarized.

All-or-none Phenomenon Either happens completely or doesn't happen at all

Refractory Period Absolute Refractory Period - opening of Na channels until Na channels begin to reset to original state Ensures each AP is separate Relative Refractory Period interval following absolute refractory period Na channels return to resting state Some K channels open, repolarization is occurring

Figure 11.14 Stimulus Absolute refractory period Relative refractory period Time (ms) Depolarization (Na + enters) Repolarization (K + leaves) After-hyperpolarization

Conduction Velocity Conduction velocities vary widely Neural pathways transmit rapidly Internal organs transmit slowly Rate of propagation depends on 2 factors- 1.Axon Diameter axons vary in diameter -Larger the diameter the faster it conducts impulses -Larger less resistance 1.Degree of Myelination unmyelinated axons channels immediately adjacent to each other conduction slow continuous conduction -Myelin sheaths rate AP propagation myelin acts as an insulator- saltatory conduction

Figure 11.15 Size of voltage Voltage-gated ion channel Stimulus Myelin sheath Stimulus Node of Ranvier Myelin sheath (a) In a bare plasma membrane (without voltage-gated channels), as on a dendrite, voltage decays because current leaks across the membrane. (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. (c) In a myelinated axon, myelin keeps current in axons (voltage doesnt decay much). APs are generated only in the nodes of Ranvier and appear to jump rapidly from node to node. 1 mm

Conduction Velocity Nerve fibers classified according to diameter, degree of myelination, and conduction Group A fibers mostly somatic sensory and motor fibers deriving the skin, skeletal muscles, and joints Largest diameter Thick myelin sheaths Impulse speed 150 m/s

Conduction Velocity Group B fibers lightly myelinated fibers of intermediate diameter Impulse speed 15 m/s Group C fibers smallest diameter Unmyelinated Incapable of saltatory conduction Impulse speed 1 m/s

Multiple Sclerosis (MS) 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

Multiple Sclerosis: Treatment Some immune systemmodifying drugs, including interferons and Copazone: Hold symptoms at bay Reduce complications Reduce disability

Nerve Fiber Classification Nerve fibers are classified according to: Diameter Degree of myelination Speed of conduction

Synapse To clasp or join Junction that mediates information transfer from one neuron to another Axodendritic Synapses synapse between axon endings of one neuron and dendrites of another neuron Axosomatic Synapses between axon endings of one neurons and cell bodies of other neurons

Figure 11.16 Dendrites Cell body Axon Axodendritic synapses Axosomatic synapses Cell body (soma) of postsynaptic neuron Axon (b) Axoaxonic synapses Axosomatic synapses (a)

Synapse Presynaptic neuron neuron conducting impulses toward the synapse Postsynaptic neuron neuron transmitting electrical signal away from the synapse

Electrical Synapse Less common variety Gap junctions found between certain body cell Contain protein channels connexons initially connect the cytoplasm of adjacent neurons and adjacent neurons allow ions and molecules to pass directly Electrically coupled Transmission rapid

Chemical Synapses Specialized for release and reception of neurotransmitter 2 parts 1. axon terminal contains tiny membrane bound sacs synaptic vesicles contain thousands of neurotransmitters 2. neurotransmitter receptor region on membrane of dendrite or cell body of postsynaptic region -Always separated by a synaptic cleft fluid filled space 30- 50 nm

Information Transfer Across Chemical Signals 1.Action potential arrives at axon terminal 2.Voltage gated Ca channels opens and Ca enters axon terminal 3.Ca entry cause neurotransmitter-containing vesicles to release their contents by exocytosis 4.Neurotransmitter diffuses across synaptic cleft and binds to specific receptors on the postsynaptic membrane 5.Binding of neurotransmitter opens ion channels, resulting in graded potentials 6.Neurotransmitter effects are terminated

Figure 11.17 Action potential arrives at axon terminal. Voltage-gated Ca 2+ channels open and Ca 2+ enters the axon terminal. Ca 2+ entry causes neurotransmitter- containing synaptic vesicles to release their contents by exocytosis. Chemical synapses transmit signals from one neuron to another using neurotransmitters. Ca 2+ Synaptic vesicles Axon terminal Mitochondrion Postsynaptic neuron Presynaptic neuron Synaptic cleft Ca 2+ Neurotransmitter diffuses across the synaptic cleft and binds to specific receptors on the postsynaptic membrane. Binding of neurotransmitter opens ion channels, resulting in graded potentials. Neurotransmitter effects are terminated by reuptake through transport proteins, enzymatic degradation, or diffusion away from the synapse. Ion movement Graded potential Reuptake Enzymatic degradation Diffusion away from synapse Postsynaptic neuron 1 2 3 4 5 6

Figure 11.17, step 1 Action potential arrives at axon terminal. Chemical synapses transmit signals from one neuron to another using neurotransmitters. Ca 2+ Synaptic vesicles Axon terminal Mitochondrion Postsynaptic neuron Presynaptic neuron Synaptic cleft Ca 2+ Postsynaptic neuron 1

Figure 11.17, step 2 Action potential arrives at axon terminal. Voltage-gated Ca 2+ channels open and Ca 2+ enters the axon terminal. Chemical synapses transmit signals from one neuron to another using neurotransmitters. Ca 2+ Synaptic vesicles Axon terminal Mitochondrion Postsynaptic neuron Presynaptic neuron Synaptic cleft Ca 2+ Postsynaptic neuron 1 2

Figure 11.17, step 3 Action potential arrives at axon terminal. Voltage-gated Ca 2+ channels open and Ca 2+ enters the axon terminal. Ca 2+ entry causes neurotransmitter- containing synaptic vesicles to release their contents by exocytosis. Chemical synapses transmit signals from one neuron to another using neurotransmitters. Ca 2+ Synaptic vesicles Axon terminal Mitochondrion Postsynaptic neuron Presynaptic neuron Synaptic cleft Ca 2+ Postsynaptic neuron 1 2 3

Figure 11.17, step 4 Action potential arrives at axon terminal. Voltage-gated Ca 2+ channels open and Ca 2+ enters the axon terminal. Ca 2+ entry causes neurotransmitter- containing synaptic vesicles to release their contents by exocytosis. Chemical synapses transmit signals from one neuron to another using neurotransmitters. Ca 2+ Synaptic vesicles Axon terminal Mitochondrion Postsynaptic neuron Presynaptic neuron Synaptic cleft Ca 2+ Neurotransmitter diffuses across the synaptic cleft and binds to specific receptors on the postsynaptic membrane. Postsynaptic neuron 1 2 3 4

Figure 11.17, step 5 Ion movement Graded potential Binding of neurotransmitter opens ion channels, resulting in graded potentials. 5

Figure 11.17, step 6 Reuptake Enzymatic degradation Diffusion away from synapse Neurotransmitter effects are terminated by reuptake through transport proteins, enzymatic degradation, or diffusion away from the synapse. 6

Figure 11.17 Action potential arrives at axon terminal. Voltage-gated Ca 2+ channels open and Ca 2+ enters the axon terminal. Ca 2+ entry causes neurotransmitter- containing synaptic vesicles to release their contents by exocytosis. Chemical synapses transmit signals from one neuron to another using neurotransmitters. Ca 2+ Synaptic vesicles Axon terminal Mitochondrion Postsynaptic neuron Presynaptic neuron Synaptic cleft Ca 2+ Neurotransmitter diffuses across the synaptic cleft and binds to specific receptors on the postsynaptic membrane. Binding of neurotransmitter opens ion channels, resulting in graded potentials. Neurotransmitter effects are terminated by reuptake through transport proteins, enzymatic degradation, or diffusion away from the synapse. Ion movement Graded potential Reuptake Enzymatic degradation Diffusion away from synapse Postsynaptic neuron 1 2 3 4 5 6

Postsynaptic Potentials and Synaptic Integration Excitatory Synapses and EPSPs Neurotransmitter binding causes depolarization on postsynaptic membrane Single type of chemically gated ion channel opens Allows Na and K to diffuse together Na influx greater than K, depolarization occurs Local graded depolarization Funtion trigger AP distally

Figure 11.18a 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 pas- sage of Na + and K +. Time (ms) (a) Excitatory postsynaptic potential (EPSP) Threshold Stimulus Membrane potential (mV)

Postsynaptic Potentials and Synaptic Integration Inhibitory Synapses and IPSPs Binding of neurotransmitters reduces postsynaptic neurons ability to fire Most induce hyperpolarization by making membrane more permeable to K or Cl Larger depolarization currents are required to induce AP

Figure 11.18b 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. Time (ms) (b) Inhibitory postsynaptic potential (IPSP) Threshold Stimulus Membrane potential (mV)

Summation EPSPs can add together or summate to influence the activity of postsynaptic neuron Temporal Summation one or more presynaptic neurons transmit impulses in rapid fire order and bursts of neurotransmitter are released in quick succession Spatial Summation postsynaptic neurons stimulated at the same time by a large number of terminals from same or different neurons

Figure 11.19a, b Threshold of axon of postsynaptic neuron Excitatory synapse 1 (E 1 ) Excitatory synapse 2 (E 2 ) Inhibitory synapse (I 1 ) Resting potential E1E1 E1E1 E1E1 E1E1 (a)No summation: 2 stimuli separated in time cause EPSPs that do not add together. (b) Temporal summation: 2 excitatory stimuli close in time cause EPSPs that add together. Time E1E1 E1E1

Figure 11.19c, d E 1 + E 2 I1I1 E 1 + I 1 (d)Spatial summation of EPSPs and IPSPs: Changes in membane potential can cancel each other out. (c) Spatial summation: 2 simultaneous stimuli at different locations cause EPSPs that add together. Time E1E1 E2E2 I1I1 E1E1

Synaptic Potential Repeated or continuous use of synapse enhances presynaptic neurons ability to excite the postsynaptic neuron producing larger than expected postsynaptic potentials

Presynaptic Inhibition Release of excitatory neurotransmitter by one neuron is inhibited by the activity of another

Neurotransmitters Language of NS Means by neurons communicate More than 50 have been identified

Classification by Chemical Structure Acetylcholine ACh 1 st identified Released at neuromuscular junctions Released by all neurons that stimulate skeletal muscle and some of ANS

Classification by Chemical Structure Biogenic Amines Catecholamines dopamines, norepinephrine, epinephrine Indolamines serotonin, histamine Broadly distributed in brain Play a role in emotional behavior and help regulate biological clock

Classification by Chemical Structure Amino Acids occur in all cells, important in biochemical reactions Gamma-aminobutyric acie Glycine Aspartate glutamate

Classification by Chemical Structure Peptides Neuropeptides strings of amino acids Substance P mediator of pain Endorphins natural opaites Gut-brain peptides produced by nonneural body tissues

Classification by Chemical Structure Purines adenosine triphophate (ATP) neurotransmitter in PNS and CNS Produces a fast excitatory response Adenosine acts outside the cell Potent inhibiter in brain

Classification by Chemical Structure Gases and Lipids Nitric Oxide and Carbon monoxide NO short lived toxic gas Variety of functions including memories CO airy messenger

Classification by Function Effects: Excitatory vs. Inhibitory Excitatory cause depolarization Inhibitory cause hyperpolarization

Classification by Function Actions: Direct vs. Indirect Direct neurotransmitters that bind to and open ion channels Indirect promote broader, long lasting effects by acting through intracellular second messengers Neuromodulator chemical messenger released by a neuron that does not directly cause EPSPs or IPSPs but instead effects the strength of synaptic transmission

Neurotransmitter Receptors Channel linked receptors ligand gated ion channels that direct transmitter action G-protein linker receptors indirect, complex, slow and often prolonged Transmembrane protein receptors

Basic Concepts of Neural Integration Neural Integration parts must be fused into a smoothly operating whole Neuronal Pool functional groups of neurons that integrate incoming information received from receptors and forward to other destinations

Figure 11.21 Presynaptic (input) fiber Facilitated zoneDischarge zoneFacilitated zone

Circuits Pattern of synaptic connections in neuronal pools Diverging Circuits one incoming fibers triggers a response in ever-increasing numbers of neurons further along pathway Converging Circuits pool receives inputs from several presynaptic neurons Reverberating, or oscillating, circuits incoming signal travels through a chain of neurons, sent continuously through circuit Parallel after discharge circuits incoming fiber stimulates several neurons arranged in parallel arrays that eventually stimulate a common output

Figure 11.22a

Figure 11.22c, d

Figure 11.22e

Figure 11.22f

Neural Processing Serial Processing whole system works in an all or nothing manner One neuron stimulates the next, which stimulates the next, etc Reflexes rapid, automatic responses to stimuli Reflex arc neural pathways of reflexes

Figure 11.23 1 2 3 4 5 Receptor Sensory neuron Integration center Motor neuron Effector Stimulus Response Spinal cord (CNS) Interneuron

Neural Processing Parallel Processing inputs are segregated into many different pathways and information delivered is dealt with simultaneously Higher level mental functioning

Developmental Aspects NS originates from a dorsal neural tube and neural crest formed from the surface of the ectoderm Neural tube becomes CNS 3 phase differentiation process 2 nd month of development 1. proliferate 2. neuroblasts migrate 3. axons connect with function targets to become neurons

Developmental Aspects Axon outgrowth and synapse formation guided by other neurons, glial cells, and chemicals Neurons that do not make the appropriate synapses die 2/3 of neurons formed in embryo undergo programmed cell death before birth

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Chapter 11: Fundamentals of the Nervous System and Nervous Tissue