1 synaptic transmission

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    Synaptic

    Transmission

    Expiratory neuron(top trace) andinspiratory neuron

    (bottom trace) werelabeled with dyeduring intracellularrecording from theventrolateralmedulla. Clearly,activity in each oneof these cells affectsactivity in the other

    one.

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    Outline

    A. Electrical synapses

    B. Overview of chemical synapses

    C. Synaptic transmission via acetylcholine

    D. Diversity of chemical synapses

    E. Norepinephrine/serotonin and depression

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    Synapses

    Cellular junctions where signals are

    transmitted from neurons to target cells

    These are communicating junctions

    Target cells: Other neurons, muscle cell,

    gland cells

    Two types of communicating junctions or

    synapses: Electrical synapses via gap

    junctions, chemical synapses involving

    neurotransmitters

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    Part A: Electrical synapses

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    Electrical synapse and gap

    junctions Recall that this involves channels comprised

    of connexons that link cells

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    Gap junctions

    A patch where cells are separated by a

    narrow gap of 2-4 nm

    Connexons, Connexins

    Each connexon is comprised of six identical

    subunits (connexins)

    Permeability of junction mediated by

    conformation of the connexons

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    Impulse transmission across

    synapses Some terminology:

    Presynaptic cellNeuron carrying action potential

    Postsynaptic cell Target cell receiving signal

    Transmission of signal can result in a depolarization ofthe postsynaptic cell - an excitatory postsynaptic

    potential (EPSP),Or hyperpolarization, or simply stabilization, of the

    membrane potential of the postsynaptic cellaninhibitory postsynaptic potential (IPSP)

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    Structure of an electrical synapse

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    Impulse transmission across

    electrical synapses is almost

    instantaneous Ions move directly from presynaptic cell to

    postsynaptic cell via gap junctions

    Transmission occurs in a few microseconds

    Over a hundred times faster than in chemical

    synapses

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    Transmission of an action potential

    across an electrical synapse

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    Under what circumstances are

    electrical synapses important? Invertebrate escape responses

    Also escape responses in vertebrates such as

    goldfish

    Large number of electrical synapses in

    fishes living at low temperature

    Can also be used to electrically couple

    groups of cells so they are synchronized

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    Summary

    Transmission of signals across electrical

    synapses is rapid This involves movement of ions via gap

    junctions

    Used when rapid conduction of signals isessential or to synchronize cells

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    Part B: Overview of chemical

    synapse

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    Structure of a chemical synapse

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    Chemical synapses

    Overall:

    Action potential of presynaptic cell causes release

    of neurotransmitter into the synaptic cleft Binding of neurotransmitter to postsynaptic cell

    results in a depolarization at excitatory synapses

    (an excitatory postsynaptic potential EPSP) or

    stabilization or hyperpolarization at inhibitory

    synapses (an IPSP).

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    chemical synapse transmission-

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    Step 1

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    Step 2

    N Ca++

    channels

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    Release

    ofsynaptic

    vesicles

    S f th l i ( ) d ki (b) f i

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    Some of the players in (a) docking (b) fusion

    preparation and (c) Ca++-sensitive exocytosis

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    Freeze-Fracture view of vesicle release

    Docking proteins and N-type Ca++ channels are visible in the picture

    at left. In the picture at right we are looking into the mouths of

    several open vesicles.

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    Vesicle Membrane Conservation: a kiss-and-run process - the motor

    protein dynamin pinches and the coating protein clathrin forms a cage

    around the membrane

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    Toxins and synaptic vesicle fusion

    Synaptobrevin and SNAP-25 are targets of the

    clostridial neurotoxins: tetanus toxin acts in the

    Central Nervous System (CNS) and botulinumtoxin acts at neuromuscular synapsesparalysis is

    caused by blockage of transmitter release.

    Neurexin is targeted by a-latrotoxin, the black

    widow spider toxin, which induces massivetransmitter release independent of Ca++ levels.

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    S 4

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    Step 4

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    Transmission of an action potential across chemical synapse

    Most of the synaptic delay (1-2 msec) is due to the

    time it takes to organize the presynaptic processes

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    Part C: Transmission via

    acetylcholine

    A fairly well-understood example

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    I. Storage of acetylcholine (ACh)

    in synaptic vesicles 40 nm diameter membrane bounded

    vesicles

    Contain 1000 to 10,000 molecules ofacetylcholine

    A single axon terminus may contain a

    million or more vesicles contacting thetarget cell at several hundred points

    Anatomy: Skeletal Muscle Synapse

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    Anatomy: Skeletal Muscle Synapse

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    Synaptic

    vesicles at

    a nerve-muscle

    synapse

    What neuromuscular synapse anatomy

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    What neuromuscular synapse anatomy

    reveals:

    The area of contact at the neuromuscular synapse is

    very extensive.

    Glia cover the area of the synapse.

    Highly specialized regions exist in both cells:

    1. The neurons have the large accumulations ofsynaptic vesicles and associated release system

    2. The muscle cell has an accumulation of receptors

    and other response elements that will allow thesignal to spread over the membrane and within the

    cell.

    Acetylcholine

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    Acetylcholine

    (ACh) and the

    neuromuscular

    synapse:

    In 1921 Otto Loewi

    showed that ACh was

    released at synapses(and also into the

    saline) by the vagus

    nerve: andtransfer of

    the solution slowed

    the heartbeat of a

    second frog heart.

    A t l h li

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    AcetylcholineACh is a transmitter that is in a class by itself:

    It is synthesized in terminals from acetyl CoA and cholineby choline acetyltransferase.

    It is packaged in vesicles in the axon terminals.

    It can bind to two distinct receptor types: nicotinic andmuscarinic. Nicotinic receptors are seen in the skeletalmuscle synapse and at synapses within the CNS.Muscarinic receptors for ACh are also seen in the CNS andat parasympathetic synapses on target tissues.

    After release, ACh is degraded by the enzymeacetylcholinesterase into acetate and choline.

    The choline is taken back into the terminal by Na+-drivenfacilitated uptake.

    Recycling is always good!

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    Recycling is always good!

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    Synthesis of acetylcholine

    Takes place in cytosol of axon terminals

    Accumulation of acetylcholine in

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    Accumulation of acetylcholine in

    synaptic vesicles

    Involves active transport

    Vacuolar-type H+ATPase

    A l ti f t l h li

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    Accumulation of acetylcholine

    V type ATPase in vesicle membrane is used

    to reduce vesicle pH Low vesicle pH powers a

    proton/neurotransmitter (NT) antiporter