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Chapter 7 Lecture Outline Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chapter 7 Outline • • • • • • • Neurons and Supporting Cells Electrical Activity in Axons The Synapse Acetylcholine as a Neurotransmitter Monoamines as Neurotransmitters Other Neurotransmitters Synaptic Integration 7-2 Neurons and Supporting Cells 7-3 Nervous System (NS) • Is divided into: – Central nervous system (CNS) • = brain and spinal cord – Peripheral nervous system (PNS) • = cranial and spinal nerves 7-4 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 7-5 Neurons 7-6 Neurons • Gather and transmit information by: – Responding to stimuli – Producing and sending electrochemical impulses – Releasing chemical messages 7-7 Neurons continued • Have a cell body, dendrites and axon – Cell body contains the nucleus 7-8 Neurons continued • Cell body is the nutritional center and makes macromolecules • Groups of cell bodies in CNS are called nuclei; in PNS are called ganglia 7-9 Neurons continued • Dendrites receive information, convey it to cell body • Axons conduct impulses away from cell body 7-10 Neurons continued • Long axon length necessitates special transport systems: – Axoplasmic flow moves soluble compounds toward nerve endings • Via rhythmic contractions of axon 7-11 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 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 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 Supporting/Glial Cells 7-15 Supporting/Glial Cells • PNS has Schwann and satellite cells – Schwann cells myelinate PNS axons 7-16 Supporting/Glial Cells continued • CNS has oligodendrocytes, microglia, astrocytes and ependymal cells 7-17 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 Myelination • In PNS each Schwann cell myelinates 1mm of 1 axon by wrapping round and round axon – Electrically insulates axon 7-19 Myelination continued • Uninsulated gap between adjacent Schwann cells is called the node of Ranvier 7-20 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 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 Neurotrophins • Promote fetal nerve growth • Required for survival of many adult neurons • Important in regeneration 7-23 Astrocytes • Most common glial cell • Involved in: – Buffering K+ levels – Recycling neurotransmitters – Regulating adult neurogenesis – Releasing transmitters that regulate neuronal activity 7-24 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 Electrical Activity in Axons 7-26 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 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 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 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 Model of a Voltage-gated Ion Channel ) 7-31 Action Potential 7-32 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 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 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 Mechanism of Action Potential continued • Depolarization and repolarization occur via diffusion – Do not require active transport – After an AP, Na+/K+ pump extrudes Na+, recovers K+ 7-36 Mechanism of Action Potential continued 7-37 APs Are All-or-None • 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 7-38 How Stimulus Intensity is Coded • Increased stimulus intensity causes more APs to be fired – Size of APs remains constant 7-39 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 Axonal Conduction 7-41 Cable Properties • Refer to how axon’s properties affect its ability to conduct current • Includes high resistance of cytoplasm – Resistance decreases as axon diameter increases • Current leaks out through ion channels 7-42 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 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 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 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 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 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 Synaptic Transmission • APs travel down axon to depolarize bouton – Open VG Ca2+ channels in bouton – Ca2+ is driven in by electrochemical gradient • Triggers exocytosis of vesicles; release of NTs 7-50 Neurotransmitter Release • Action potentials reach the axon terminal • Ca2+ enters axon terminal via voltage gated channels • Ca2+ binds to sensor protein in cytoplasm • Ca2+ -protein complex stimulates fusion and exocytosis of neurotransmitter • Neurotransmitter is released from the vesicles into synapse 7-51 Synaptic Transmission continued • Neurotranmitter diffuses across cleft – Binds to receptor proteins on postsynaptic membrane • Opening chemically-regulated ion channels – Depolarizing channels cause EPSPs (excitatory postsynaptic potentials) – Hyperpolarizing channels cause IPSPs (inhibitory postsynaptic potentials) – These affect VG channels in postsynaptic cell 7-52 Synaptic Transmission continued • EPSPs and IPSPs summate • If MP in postsynaptic cell reaches threshold at the axon hillock, a new AP is generated – axon hillock has many VG channels and is site where APs are normally initiated 7-53 Synaptic Transmission continued 7-54 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 Ligand-Gated Channels • Contain both a NT receptor site and an ion channel • Open when ligand (NT) binds 7-56 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 G Protein-Coupled Channels • NT receptor is not part of the ion channel – Is a 1 subunit membrane polypeptide – Activates ion channel indirectly through G-proteins 7-58 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 Acetylcholinesterase (AChE) • Inactivates ACh, terminating its action; located in cleft 7-60 Neurotransmitters 7-61 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 Neuromuscular Junction 7-62 Monoamine NTs • Include serotonin, norepinephrine and dopamine • Serotonin is derived from tryptophan • Norepinephrine and dopamine are derived from tyrosine – Called catecholamines 7-63 Monoamine NTs continued • After release, are mostly inactivated by: – Presynaptic reuptake – And breakdown by monoamine oxidase (MAO) • MAO inhibitors are antidepressants 7-64 Monoamine NTs continued • Their receptors activate G-protein cascade to affect ion channels 7-65 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 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 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 Amino Acids NTs • Glutamic acid and aspartic acid are major CNS excitatory NTs • Glycine is an inhibitory NT – Opens Cl- channels which hyperpolarize – Strychnine blocks glycine receptors • Causes spastic paralysis • GABA (gamma-aminobutyric acid) is most common NT in brain – Inhibitory, opens Cl- channels – These degenerate in Huntington’s disease (see Ch 3) 7-69 Polypeptide NTs (neuropeptides) • Cause wide range of effects • Not thought to open ion channels • Many are neuromodulators – Involved in learning and neural plasticity • Most neurons release a classical and polypeptide NT 7-70 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 7-71 Polypeptide NTs (neuropeptides) continued • Neuropeptide Y is most common neuropeptide – Inhibits glutamate in hippocampus – Powerful stimulator of appetite 7-72 Polypeptide Neurotranmitters (neuropeptides) continued • Endocannabinoids - similar to THC in marijuana – Are the only lipid Neurotranmitter – Not stored in vesicles; are produced from lipids of the plasma membrane – Are retrograde Neurotransmitters: they act on neuron that releases them • And thereby may be involved in learning – Like THC, they stimulate appetite 7-73 Gaseous NTs • NO and CO are gaseous NTs – Act through cGMP second messenger system – NO causes smooth muscle relaxation • Viagra increases NO • In some cases it may act as a retrograde NT 7-74 Synaptic Integration 7-75 EPSPs • Graded in magnitude • Have no threshold • Cause depolarization • Summate • Have no refractory period 7-76 Spatial Summation • Cable properties cause EPSPs to fade quickly over time and distance • Spatial summation takes place when EPSPs from different synapses occur in postsynaptic cell at same time 7-77 Temporal Summation • Temporal summation occurs because EPSPs that occur closely in time can sum before they fade 7-78 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 7-79 Synaptic Inhibition • Postsynaptic inhibition – GABA and 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 7-80