Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chapter 7 The Nervous System: Neurons and Synapses 7-1

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Nervous System (NS)  Is divided into:  Central nervous system (CNS)  = brain and spinal cord, eye  Peripheral nervous system (PNS)  = cranial and spinal nerves  Enteuic ns (gut)  Autonomic- parasympathetic 7-4

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Nervous System (NS) continued  Consists of 2 kinds of cells:  Neurons and supporting cells (= glial cells)  Neurons are functional units of NS  Glial cells maintain homeostasis  Are 5X more common than neurons  Are important for myelination  Structural support  neural survival-neurotrophin  neurotoxicity protection 7-5

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Neurons continued  Have a cell body, dendrites and axon  Cell body contains the nucleus 7-8

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Neurons  Gather and transmit information by:  Responding to stimuli  Producing and sending electrochemical impulses  Releasing chemical messages 7-7

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Neurons continued  Dendrites receive information, convey it to cell body  Axons conduct impulses away from cell body 7-10

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Neurons continued  Axonal transport moves large and insoluble compounds bidirectionally along microtubules; very fast  Anterograde transport moves materials away from cell body  Uses the molecular motor kinesin  Retrograde transport moves materials toward cell body  Uses the molecular motor dynein  Viruses and toxins can enter CNS this way 7-12

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Functional Classification of Neurons  Sensory/Afferent neurons conduct impulses into CNS  Motor/Efferent neurons carry impulses out of CNS  Association/ Interneurons integrate NS activity  Located entirely inside CNS 7-13

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Structural Classification of Neurons  Pseudounipolar:  Cell body sits along side of single process  e.g. sensory neurons  Bipolar:  Dendrite and axon arise from opposite ends of cell body  e.g. retinal neurons  Multipolar:  Have many dendrites and one axon  e.g. motor neurons 7-14

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Supporting/Glial Cells  PNS has Schwann and satellite cells  Schwann cells myelinate PNS axons 7-16

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Supporting/Glial Cells continued  CNS has oligodendrocytes, microglia, astrocytes and ependymal cells 7-17

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Supporting/Glial Cells continued  Each oligodendrocyte myelinates several CNS axons  Ependymal cells appear to be neural stem cells  Other glial cells are involved in NS maintenance 7-18

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Myelination  In PNS each Schwann cell myelinates 1mm of 1 axon by wrapping round and round axon  Electrically insulates axon 7-19

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Myelination continued  Uninsulated gap between adjacent Schwann cells is called the node of Ranvier 7-20

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Axon Regeneration  Occurs much more readily in PNS than CNS  Oligodendrocytes produce proteins that inhibit regrowth  And form glial scar tissue that blocks regrowth 7-21

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Nerve Regeneration continued  When axon in PNS is severed:  Distal part of axon degenerates  Schwann cells survive; form regeneration tube  Tube releases chemicals that attract growing axon  Tube guides regrowing axon to synaptic site 7-22

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Neurotrophins  Promote fetal nerve growth  Required for survival of many adult neurons  Important in regeneration  NGF-Nerve Growth Factor  Read the abstract and intro to the paper on WEBCT… 7-23

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Astrocytes  Most common glial cell  Involved in:  Buffering K+ levels  Recycling neurotransmitters  Regulating adult neurogenesis  Releasing transmitters that regulate neuronal activity 7-24

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Blood-Brain Barrier  Allows only certain compounds to enter brain  Formed by capillary specializations in brain  That appear to be induced by astrocytes  Capillaries are not as leaky as those in body  Gaps between adjacent cells are closed by tight junctions 7-25

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Resting Membrane Potential (RMP)  At rest, all cells have a negative internal charge and unequal distribution of ions:  Results from:  Large cations being trapped inside cell  Na+/K+ pump and limited permeability keep Na+ high outside cell  K+ is very permeable and is high inside cell  Attracted by negative charges inside 7-27

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Excitability  Excitable cells can discharge their RMP quickly  By rapid changes in permeability to ions  Neurons and muscles do this to generate and conduct impulses 7-28

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Membrane Potential (MP) Changes  Measured by placing 1 electrode inside cell and 1 outside  Depolarization occurs when MP becomes more positive  Hyperpolarization: MP becomes more negative than RMP  Repolarization: MP returns to RMP 7-29

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Membrane Ion Channels  MP changes occur by ion flow through membrane channels  Some channels are normally open; some closed  K + leakage channels are always open  Closed channels have molecular gates that can be opened  Voltage-gated (VG) channels are opened by depolarization  VG K + channels are closed in resting cells  Na + channels are VG; closed in resting cells 7-30

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Model of a Voltage-gated Ion Channel ) 7-31

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. The Action Potential (AP)  Is a wave of MP change that sweeps along the axon from soma to synapse  Wave is formed by rapid depolarization of the membrane by Na + influx; followed by rapid repolarization by K + efflux 7-33

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Mechanism of Action Potential  Depolarization:  At threshold, VG Na + channels open  Na+ driven inward by its electrochemical gradient  This adds to depolarization, opens more channels  Termed a positive feedback loop  Causes a rapid change in MP from –70 to +30 mV 7-34

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Mechanism of Action Potential continued  Repolarization:  VG Na + channels close; VG K + channels open  Electrochemical gradient drives K + outward  Repolarizes axon back to RMP 7-35

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  Depolarization and repolarization occur via diffusion  Do not require active transport  After an AP, Na + /K + pump extrudes Na +, recovers K + Mechanism of Action Potential continued 7-36

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Mechanism of Action Potential continued 7-37

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  When MP reaches threshold an AP is irreversibly fired  Because positive feedback opens more and more Na + channels  Shortly after opening, Na + channels close  and become inactivated until repolarization APs Are All-or-None 7-38

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  Increased stimulus intensity causes more APs to be fired  Size of APs remains constant How Stimulus Intensity is Coded 7-39

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Refractory Periods  Absolute refractory period:  Membrane cannot produce another AP because Na + channels are inactivated  Relative refractory period occurs when VG K + channels are open, making it harder to depolarize to threshold 7-40

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Conduction in an Unmyelinated Axon  After axon hillock reaches threshold and fires AP, its Na + influx depolarizes adjacent regions to threshold  Generating a new AP  Process repeats all along axon  So AP amplitude is always same  Conduction is slow 7-43

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Conduction in Myelinated Axon  Ions can't flow across myelinated membrane  Thus no APs occur under myelin  and no current leaks  This increases current spread 7-44

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Conduction in Myelinated Axon continued  Gaps in myelin are called Nodes of Ranvier  APs occur only at nodes  VG Na+ channels are present only at nodes  Current from AP at 1 node can depolarize next node to threshold  Fast because APs skip from node to node  Called saltatory conduction 7-45

Synaptic Transmission 7-46

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Synapse  Is a functional connection between a neuron (presynaptic) and another cell (postsynaptic)  There are chemical and electrical synapses  Synaptic transmission at chemical synapses is via neurotransmitters (NT)  Electrical synapses are rare in NS 7-47

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Electrical Synapse  Depolarization flows from presynaptic into postsynaptic cell through channels called gap junctions  Formed by connexin proteins  Found in smooth and cardiac muscles, brain, and glial cells 7-48

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chemical Synapse  Synaptic cleft separates terminal bouton of presynaptic from postsynaptic cell  NTs are in synaptic vesicles  Vesicles fuse with bouton membrane; release NT by exocytosis  Amount of NT released depends upon frequency of APs 7-49

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Synaptic Transmission  APs travel down axon to depolarize bouton  Open VG Ca 2+ channels in bouton  Ca 2+ is driven in by electrochemical gradient  Triggers exocytosis of vesicles; release of NTs 7-50

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Synaptic Transmission continued 7-54

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Acetylcholine (ACh)  Most widely used NT  Used in brain and ANS; used at all neuromuscular junctions  Has nicotinic and muscarinic receptor subtypes  These can be excitatory or inhibitory 7-55

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Nicotinic ACh Channel  Formed by 5 polypeptide subunits  2 subunits contain ACh binding sites  Opens when 2 AChs bind  Permits diffusion of Na + into and K + out of postsynaptic cell  Inward flow of Na + dominates  Produces EPSPs 7-57

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Muscarinic ACh Channel  Binding of 1 ACh activates G-protein cascade which affects gated K+ channels  Opens some, causing hyperpolarization  Closes others, causing depolarization 7-59

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Acetylcholinesterase (AChE)  Inactivates ACh, terminating its action; located in cleft 7-60

Neurotransmitters 7-61

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Acetylcholine in the PNS  Cholinergic neurons use acetylcholine as NT  The large synapses on skeletal muscle are termed end plates or neuromuscular junctions (NMJ)  Produce large EPSPs called end-plate potentials  Open VG channels beneath end plate  Cause muscle contraction  Curare blocks ACh action at NMJ 7-62

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Monoamine NTs  Include serotonin, norepinephrine and dopamine  Serotonin is derived from tryptophan  Norepinephrine and dopamine are derived from tyrosine  Called catecholamines 7-63

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Monoamine NTs continued  After release, are mostly inactivated by:  Presynaptic reuptake  And breakdown by monoamine oxidase (MAO)  MAO inhibitors are antidepressants -TRANSPORTER 7-64

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Serotonin  Involved in regulation of mood, behavior, appetite and cerebral circulation  LSD is structurally similar  SSRIs (serotonin-specific reuptake inhibitors) are antidepressants  e.g., Prozac, Zoloft, Paxil, Luvox  Block reuptake of serotonin, prolonging its action 7-66

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Dopamine  There are 2 major dopamine systems in brain  Nigrostriatal dopamine system originates in the substantia nigra and is involved in motor control  Degeneration of this system causes Parkinson's disease  Mesolimbic dopamine system is involved in behavior and emotional reward  Most addictions activate this system  Overactivity contributes to schizophrenia  Which is treated by anti-dopamine drugs 7-67

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Norepinephrine (NE)  Used in PNS and CNS  In PNS is a sympathetic NT  In CNS affects general level of arousal  Amphetamines stimulate NE pathways 7-68

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Polypeptide NTs (neuropeptides) continued  CCK promotes satiety following meals  Substance P is a pain NT  Endorphins, enkephalins and dynorphin are endogenous opioid NTs  Promote analgesia and mediate many placebo effects  Effects are blocked by naloxone, an opiate antagonist  Neuropeptide Y is most common neuropeptide  Inhibits glutamate in hippocampus  Powerful stimulator of appetite 7-71

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Polypeptide NTs (neuropeptides) continued  Endocannabinoids - similar to THC in marijuana  Are the only lipid NTs  Not stored in vesicles; are produced from lipids of the plasma membrane  Are retrograde NTs: they act on neuron that releases them  And thereby may be involved in learning  Like THC, they stimulate appetite 7-73