Synaptic transmission 1
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.
Outline
•
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A. Electrical synapses
B. Overview of chemical synapses
C. Synaptic transmission via acetylcholine
D. Diversity of chemical synapses
E. Norepinephrine/serotonin and depression
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
Part A: Electrical synapses
Electrical synapse and gap
junctions
• Recall that this involves channels comprised
of connexons that link cells
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
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)
Structure of an electrical synapse
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
Transmission of an action potential
across an electrical synapse
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
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
Part B: Overview of chemical
synapse
Structure of a chemical synapse
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).
chemical synapse transmission-
Step 1
Step 2
N Ca++
channels
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
ready 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 vesicle’s location – this Ca++ causes vesicle fusion –
transmitter is released into synaptic cleft.
Release
of
synaptic
vesicles
Some of the “players” in (a) docking (b) fusion
preparation and (c) Ca++-sensitive exocytosis
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.
Vesicle Membrane Conservation: a kiss-and-run process - the motor
protein dynamin pinches and the coating protein clathrin forms a cage
around the membrane…
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.
Step 3
Step 4
Step 5
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
Part C: Transmission via
acetylcholine
A fairly well-understood example
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
Anatomy: Skeletal Muscle Synapse
Synaptic
vesicles at
a nervemuscle
synapse
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 of
synaptic vesicles and associated release system
2. 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.
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.
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.
Recycling is always good!
Synthesis of acetylcholine
• Takes place in cytosol of axon terminals
Accumulation of acetylcholine in
synaptic vesicles
• Involves active transport
Vacuolar-type H+ATPase
Accumulation of acetylcholine
• V type ATPase in vesicle membrane is used
to reduce vesicle pH
• Low vesicle pH powers a
proton/neurotransmitter (NT) antiporter