1 Synaptic Transmission
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Transcript of 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