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    Copyright 2007 Wolters Kluwer Health | Lippincott Williams & Wilkins

    Neuroscience: Exploring the Brain, 3e

    Chapter 5: Synaptic Transmission

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    Introduction

    Synaptic Transmission

    Information transfer at a synapse

    Plays role in all the operations of the nervous system

    1897: Charles Sherrington-synapse

    Chemical and electrical synapses

    1921- Otto Loewi

    1959- Furshpan and Potter

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    Types of Synapses

    Direction of Information Flow

    In one direction: Neuron to target cell

    First neuron = Presynaptic neuron

    Target cell = Postsynaptic neuron

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    Electrical Synapses

    Gap junction

    Channel

    Connexon- formed by six connexins

    Cells are said to be electrically coupled

    Flow of ions from cytoplasm to cytoplasm

    Types of Synapses

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    INSERT FIG. 5.1 (Yes, deliberately out of order)

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    Types of Synapses

    Electrical Synapses (Contd)

    Very fast transmission

    Postsynaptic potentials (PSPs)

    Synaptic integration: Several PSPs occurringsimultaneously to excite a neuron (i.e. causes AP)

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    Types of Synapses

    Chemical Synapses

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    Types of Synapses

    Chemical Synapses

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    CNS Synapses (Examples)

    Axodendritic: Axon to dendrite

    Axosomatic: Axon to cell body

    Axoaxonic: Axon to axon

    Dendrodendritic: Dendrite to dendrite

    Types of Synapses

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    CNS Synapses (Examples)

    Grays Type I: Asymmetrical, excitatory

    Grays Type II: Symmetrical, inhibitory

    Types of Synapses

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    The Neuromuscular Junction

    (NMJ) Studies of NMJ established

    principles of synaptictransmission

    Types of Synapses

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    Principles of Chemical SynapticTransmission

    Basic Steps

    Neurotransmitter synthesis

    Load neurotransmitter into synaptic vesicles

    Depolarization Vesicles fuse to presynaptic terminal

    Neurotransmitter spills into synaptic cleft

    Binds to postsynaptic receptors

    Biochemical/Electrical response elicited in postsynaptic cell

    Removal of neurotransmitter from synaptic cleft

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    Neurotransmitters

    Amino acids: Small organic molecules

    e.g., Glutamate, Glycine, GABA

    Amines: Small organic molecules

    e.g., Dopamine, Acetylcholine, Histamine

    Peptides: Short amino acid chains (i.e. proteins)stored in and released from secretory granules

    e.g., Dynorphin, Enkephalins

    Principles of Chemical SynapticTransmission

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    Neurotransmitters

    Principles of Chemical SynapticTransmission

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    Neurotransmitter Synthesis and Storage

    Amines, amino acids, peptides

    Principles of Chemical SynapticTransmission

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    Neurotransmitter Release

    Exocytosis: Process by which vesicles release theircontents

    Principles of Chemical SynapticTransmission

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    Neurotransmitter Release (Contd)

    Mechanisms

    Process of exocytosis stimulated by release ofintracellular calcium, [Ca2+]i

    Proteins alter conformation - activated

    Vesicle membrane incorporated into presynapticmembrane

    Neurotransmitter released

    Vesicle membrane recovered by endocytosis

    Principles of Chemical SynapticTransmission

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    Neurotransmitter receptors:

    Ionotropic: Transmitter-gated ion channels

    Principles of Chemical SynapticTransmission

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    Metabotropic: G-protein-coupled receptor

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    Excitatory and Inhibitory Postsynaptic Potentials:

    EPSP:Transient postsynaptic membrane depolarization bypresynaptic release of neurotransmitter

    IPSP: Transient hyperpolarization of postsynaptic membranepotential caused by presynaptic release of neurotransmitter

    Reversal potential concept

    Principles of Chemical SynapticTransmission

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    Neurotransmitter Recovery and Degradation

    Diffusion: Away from the synapse

    Reuptake: Neurotransmitter re-enters presynapticaxon terminal

    Enzymatic destruction inside terminal cytosol orsynaptic cleft

    Desensitization: e.g., AChE cleaves Ach to inactivestate

    Principles of Chemical SynapticTransmission

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    Neuropharmacology

    Effect of drugs on nervous system tissue

    Receptor antagonists: Inhibitors of neurotransmitterreceptors

    Curare

    Receptor agonists: Mimic actions of naturallyoccurring neurotransmitters

    Nicotine

    Defective neurotransmission: Root cause ofneurological and psychiatric disorders

    Principles of Chemical SynapticTransmission

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    Principles of Synaptic Integration Synaptic Integration

    Process by which multiple synaptic potentialscombine within one postsynaptic neuron

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    Quantal Analysis of EPSPs

    Synaptic vesicles: Elementary units of synaptic

    transmission Quantum: An indivisible unit

    Miniature postsynaptic potential (mini)

    Quantal analysis: Used to determine number of

    vesicles that release during neurotransmission

    Neuromuscular junction: About 200 synaptic vesicles,EPSP of 40mV or more

    CNS synapse: Single vesicle, EPSP of few tenths of amillivolt

    Principles of Synaptic Integration

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    EPSP Summation

    Allows for neurons to perform sophisticatedcomputations

    Integration: EPSPs added together to producesignificant postsynaptic depolarization

    Spatial: EPSP generated simultaneously in differentspaces

    Temporal: EPSP generated at same synapse in rapidsuccession

    Principles of Synaptic Integration

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    The Contribution of Dendritic Properties to SynapticIntegration

    Dendrite as a straight cable Membrane depolarization falls off exponentially with

    increasing distance

    Vx = Vo/ex/

    Dendritic length constant ()

    In reality, dendrites are very elaborate structuresthat contribute to more complex integrativeproperties

    Principles of Synaptic Integration

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    The Contribution ofDendritic Properties to

    Synaptic Integration

    Principles of Synaptic Integration

    Vx=V

    o* e-x/

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    Excitable Dendrites

    Dendrites of neurons: voltage-gated sodium,

    calcium, and potassium channels

    Can act as amplifiers (vs. passive)

    Dendritic sodium channels: May carry electricalsignals in opposite direction, from soma outwardalong dendrites

    Principles of Synaptic Integration

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    Inhibition

    Action of synapses to take membrane potential away

    from action potential threshold

    Exerts powerful control over neuron output

    Principles of Synaptic Integration

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    IPSPs and Shunting Inhibition

    Excitatory vs. inhibitory synapses: Bind different

    neurotransmitters, allow different ions to pass throughchannels

    Membrane potential more negative than -65mV =hyperpolarizing IPSP

    Shunting Inhibition: Inhibiting current flow from soma toaxon hillock

    Principles of Synaptic Integration

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    Shunting Inhibition: Inhibiting current flow from soma toaxon hillock

    Principles ofSynaptic Integration

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    The Geometry of Excitatory and Inhibitory Synapses

    Excitatory synapses

    Grays type I morphology

    Spines: Excitatory synapses

    Inhibitory synapses

    Grays type II morphology

    Clustered on soma and near axon hillock

    Principles of Synaptic Integration

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    Concluding Remarks

    Chemical synaptic transmission

    Rich diversity allows for complex behavior

    Provides explanations for drug effects

    Defective transmission is the basis for manyneurological and psychiatric disorders

    Key to understanding the neural basis of learningand memory

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    End of Presentation

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    Principles of Synaptic Integration

    Modulation

    Synaptic transmission thatmodifies effectiveness ofEPSPs generated by othersynapses with transmitter-gated ion channels

    Example: Activating NE receptor