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. Chapter 7 Outline  Structure of NS  Neurons  Supporting/Glial Cells  Membrane Potential  Action Potential  Axonal Conduction  Synaptic Transmission  Neurotransmitters  Synaptic Integration 7-2

Structure of Nervous System 7-3

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Nervous System (NS)  Is divided into:  Central nervous system (CNS)  = brain & spinal cord  Peripheral nervous system (PNS)  = cranial & spinal nerves 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 & supporting cells (= glial cells)  Neurons are functional units of NS  Supporting cells maintain homeostasis  Are 5X more common than neurons 7-5

Neurons 7-6

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

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

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Neurons continued  Cell body makes macromolecules  Groups of cell bodies in CNS are called nuclei; in PNS are called ganglia Fig

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 Fig

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Neurons continued  Axon length necessitates special transport systems:  Axoplasmic flow moves soluble compounds toward nerve endings  Via rhythmic contractions of axon  Axonal transport moves large & insoluble compounds bidirectionally  Along microtubules; very fast  Viruses & toxins enter CNS this way 7-11

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 Fig

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 & axon arise from opposite ends of cell body  e.g. retinal neurons  Multipolar:  Have many dendrites & one axon  e.g. motor neurons Fig

Supporting/Glial Cells 7-14

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

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

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

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 & round axon  Electrically insulates axon Fig

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Myelination continued Fig 7.2  Uninsulated gap between adjacent Schwann cells is called node of Ranvier 7-19

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Nerve Regeneration  Occurs much more readily in PNS than CNS  Oligodendrocytes produce proteins that inhibit regrowth 7-20

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 Fig

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 7-22

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Astrocytes  Most common glial cell  Involved in:  Inducing capillaries to form blood-brain barrier  Buffering K+ levels  Recycling neurotransmitters  Regulating adult neurogenesis Fig

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  Capillaries are not as leaky as those in body  Do not have gaps between adjacent cells  Closed by tight junctions 7-24

Membrane Potential 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 & unequal distribution of ions:  Results from:  Large cations being trapped inside cell  Na+/K+ pump & limited permeability keep Na+ high outside cell  K+ is very permeable & is high inside cell  Attracted by negative charges inside 7-26

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 & muscles do this to generate & conduct impulses 7-27

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

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  Closed channels have molecular gates that can be opened  Voltage-gated (VG) channels are opened by depolarization  1 type of K + channel is always open; other type is VG & is closed in resting cell  Na + channels are VG; closed in resting cells 7-29

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

Action Potential 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 Fig

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 7-33

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 7-34

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  Depolarization & repolarization occur via diffusion  Do not require active transport  After an AP, Na + /K + pump extrudes Na +, recovers K + Mechanism of Action Potential continued 7-35

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 & more Na + channels  Shortly after opening, Na + channels close  & become inactivated until repolarization APs Are All-or-None 7-36

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 7-37

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 Fig

Axonal Conduction 7-39

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Cable Properties  Refers to ability of axon to conduct current  Axon cable properties are poor because:  Cytoplasm has high resistance  Though resistance decreases as axon diameter increases  Current leaks out through ion channels 7-40

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Conduction in an Unmyelinated Axon  After axon hillock reaches threshold & 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 Fig

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  & no current leaks  Increases current spread Fig

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  Current from AP at 1 node can depolarize next node to threshold  Fast because APs skip from node to node  Called Saltatory conduction Fig

Synaptic Transmission 7-44

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Synapse  Is a functional connection between a neuron (presynaptic) & another cell (postsynaptic)  There are chemical & electrical synapses  Synaptic transmission in chemicals is via neurotransmitters (NT)  Electricals are rare in NS 7-45

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 & cardiac muscles, brain, and glial cells Fig

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chemical Synapse Fig 7.22  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 7-47

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+ driven in by electrochemical gradient  Triggers exocytosis of vesicles; release of NTs 7-48

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Neurotransmitter Release  Is rapid because vesicles are already docked at release sites on bouton before APs arrive  Docked vesicles are part of fusion complex  Ca 2+ triggers exocytosis of vesicles 7-49

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Synaptic Transmission continued  NT (ligand) diffuses across cleft  Binds to receptor proteins on postsynaptic membrane  Chemically-regulated ion channels open  Depolarizing channels cause EPSPs (excitatory postsynaptic potentials)  Hyperpolarizing channels cause IPSPs (inhibitory postsynaptic potentials)  These affect VG channels in postsynaptic cell 7-50

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Synaptic Transmission continued  EPSPs & IPSPs summate  If MP in postsynaptic cell reaches threshold, a new AP is generated Fig

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Acetylcholine (ACh)  Most widely used NT  NT at all neuromuscular junctions  Used in brain  Used in ANS  Where can be excitatory or inhibitory  Depending on receptor subtype  Nicotinic or muscarinic 7-52

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Ligand-Operated Channels  Ion channel runs through receptor  Opens when ligand (NT) binds 7-53

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 Fig

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. G Protein-Operated Channels  Receptor is not part of the ion channel  Is a 1 subunit membrane polypeptide  Activates channel indirectly through G-proteins 7-55

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

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

Neurotransmitters 7-58

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Neuromuscular Junction (NMJ)  Cholinergic neurons use acetylcholine as NT  The large synapses on skeletal muscle are termed end plates or neuromuscular junctions  Produce large EPSPs called end-plate potentials  Open VG channels beneath end plate  Cause muscle contraction  Curare blocks ACh action at NMJ 7-59

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Monoamine NTs  Receptors activate G-protein cascade to affect ion channels Fig

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Monoamine NTs continued  Include serotonin, norepinephrine, & dopamine,  Serotonin is derived from tryptophan  Norepi & dopamine are derived from tyrosine  Called catecholamines 7-61

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

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Serotonin  Involved in regulation of mood, behavior, appetite, & cerebral circulation  LSD is structurally similar  SSRIs (serotonin-specific reuptake inhibitors) include antidepressants  Prozac, Zolof, Paxil, Luvox  Block reuptake of serotonin, prolonging its action 7-63

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Dopamine  Involved in motor control & emotional reward  Degeneration of dopamine motor system neurons causes Parkinson's disease  Reward system is involved in addiction  Schizophrenia treated by anti-dopamine drugs 7-64

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Norepinephrine (NE)  Used in PNS & CNS  In PNS is a sympathetic NT  In CNS affects general level of arousal  Amphetamines stimulate NE pathways 7-65

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Amino Acids NTs  Glutamic acid & aspartic acid are major CNS excitatory NTs  Glycine is an inhibitory NT  Opens Cl - channels which hyperpolarize  Strychnine blocks glycine receptors  GABA (gamma-aminobutyric acid) is most common NT in brain  Inhibitory, opens Cl - channels 7-66

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Polypeptide NTs (neuropeptides)  Cause wide range of effects  Not thought to open ion channels  Many are neuromodulators  Involved in learning & neural plasticity  Most neurons can release a classical & polypeptide NT 7-67

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Polypeptide NTs (neuropeptides)  CCK promotes satiety following meals  Substance P is a pain NT  Endorphins, enkephalins, & dynorphin are analgesics  Effects are blocked by naloxone, an opiate antagonist 7-68

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Polypeptide NTs (neuropeptides)  Neuropeptide Y is most common neuropeptide  Inhibits glutamate in hippocampus  Powerful stimulator of appetite  Endocannabinoids - similar to THC in marijuana  Only lipid NTs  Have analgesic effects  NO & CO are gaseous NTs  Act through cGMP second messenger system  NO causes smooth muscle relaxation  Viagra increases NO 7-69

Synaptic Integration 7-70

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. EPSPs  Graded in magnitude  Have no threshold  Cause depolarization  Summate  Have no refractory period Fig

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Spatial Summation  Cable properties cause EPSPs to fade quickly over time & distance  Spatial summation takes place when EPSPs from different synapses occur in postsynaptic cell at same time Fig

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Temporal Summation  Temporal summation occurs because EPSPs that occur closely in time can sum before they fade 7-73

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Synaptic Plasticity  Repeated use of a synapse can increase or decrease its ease of transmission  = synaptic facilitation or synaptic depression  High frequency stimulation often causes enhanced excitability  Called long-term potentiation  Believed to underlie learning 7-74

Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Synaptic Inhibition  Postsynaptic inhibition  GABA & glycine produce IPSPs  IPSPs dampen EPSPs  Making it harder to reach threshold  Presynaptic inhibition:  Occurs when 1 neuron synapses onto axon or bouton of another neuron, inhibiting release of its NT Fig