Synaptic transmission 1

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Synaptic transmission 1
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Synaptic Transmission

• Expiratory neuron (top trace) and inspiratory
  neuron (bottom trace) were labeled with dye
  during intracellular recording from the
  ventrolateral medulla. Clearly, activity in each
  one of these cells affects activity 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 cell
• Neuron carrying action potential
• Postsynaptic cell
• Target cell receiving signal
• Transmission of signal can result in a
  depolarization of the postsynaptic cell - an
  excitatory postsynaptic potential (EPSP),
• Or hyperpolarization, or simply stabilization, of
  the membrane potential of the postsynaptic cell
  an inhibitory 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 is
  essential 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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How vesicle fusion occurs Reserve pool of
vesicles is free in synaptic terminal but these
have to undergo docking and priming to be ready
to release Some vesicles are attached to the
presynaptic membrane by connections between
specific proteins on vesicle and counterparts on
presynaptic membrane- at least 6 different
proteins are believed to be involved. These are
primed. They have joined the reserve pool. To
enter the ready-to-release pool, a primed vesicle
must be docked by becoming associated with n-type
Ca channels at the presynaptic
membrane. Depolarization opens the Ca channels
tiny geysers of Ca occurs at that vesicles
location this Ca causes vesicle fusion
transmitter is released into synaptic cleft.
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Release of synaptic vesicles
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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 botulinum
  toxin acts at neuromuscular synapses paralysis
  is caused by blockage of transmitter release.
• Neurexin is targeted by a-latrotoxin, the black
  widow spider toxin, which induces massive
  transmitter release independent of Ca levels.

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Step 3
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Step 4
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Step 5
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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 of acetylcholine
• A single axon terminus may contain a million or
  more vesicles contacting the target cell at
  several hundred points

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Anatomy Skeletal Muscle Synapse
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Synaptic vesicles at a nerve-muscle synapse
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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
• The neurons have the large accumulations of
  synaptic vesicles and associated release system
• The muscle cell has an accumulation of receptors
  and other response elements that will allow the
  signal to spread over the membrane and within the
  cell.

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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 and transfer of the solution slowed
  the heartbeat of a second frog heart.

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Acetylcholine

• ACh is a transmitter that is in a class by
  itself
• It is synthesized in terminals from acetyl CoA
  and choline by choline acetyltransferase.
• It is packaged in vesicles in the axon terminals.
• It can bind to two distinct receptor types
  nicotinic and muscarinic. Nicotinic receptors are
  seen in the skeletal muscle synapse and at
  synapses within the CNS. Muscarinic receptors
  for ACh are also seen in the CNS and at
  parasympathetic synapses on target tissues.
• After release, ACh is degraded by the enzyme
  acetylcholinesterase into acetate and choline.
• The choline is taken back into the terminal by
  Na-driven facilitated uptake.

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Recycling is always good!
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Synthesis of acetylcholine

• Takes place in cytosol of axon terminals

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Accumulation of acetylcholine in synaptic vesicles

• Involves active transport

Vacuolar-type HATPase
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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