Physiology Lecture 3 Notes: Synaptic Transmission

Basic CNS Neuron

 Cell body (soma, perikaryon): meets the metabolic needs of the cell and maintains the
ionic gradients
 Dendrites: are the input region of the cell, they collect information from other cells and
convey the signals to the cell body
 Axon hillock (Integrative Segment)- action potentials are initiated here due to the highest
concentration of voltage-gated Na+ channels, which means a small depolarization has a
large effect
 Axon- one axon per cell that exits the soma at the axon hillock and rapidly transmits
action potentials from the soma to neuron output areas
 Synapses- regions of the cell where information is transferred (neuron to neuron or
neuron to muscle)
o Dendritic input synapses- receive information from other neurons
o Output synapse- distal end of axon and transmit information to other neurons or to
muscles

Types of Synapses
 Electrical: direct spread of ionic current between axoplasm of the pre and postsynaptic
cells
o Axoplasm of pre- and postsynaptic cells are connected by connexons in the
cytoplasm
 Connexons are rectifying (current moves in one direction) or non-
rectifying (current can go in both directions)
o Used when don’t need to make quick decisions
 Cardiac and smooth muscle, and gut
 Intercalated discs hold muscles together at gap junctions in cardiac
muscle cells
o Electrical synapse is made up of gap junctions between cells that are very close
together
 Chemical: chemical transmitter is released from presynaptic cell and diffuses across the
synaptic cleft to interact with (change permeability of) receptors on the postsynaptic cell
o Used in CNS where behavior must be quick and flexible
o Capable of amplification where one presynaptic cell can activate as many as
several hundred postsynaptic cells

Chemical Synapse
1. Inactive transmitter is synthesized and stored in vesicles
2. Action potential invades the presynaptic terminal
3. Depolarization of presynaptic terminal causes opening of voltage-gated Ca2+ channels
a. Moving vesicle toward synapse
b. Dumping transmitter that is already at the synapse
4. Transmitter is released into synaptic cleft via exocytosis
5. Transmitter binds to receptor molecules in postsynaptic membrane
a. Opening postsynaptic channels
 b. Closing postsynaptic channels
6. Depending on the synapse the postsynaptic cell can depolarize or hyperpolarize

Types of Transmitters
1. Acetylcholine
2. Amines
3. Amino Acids
4. Purines

Transmitter Synthesis
 Cell body- amino acids are made and packaged into vesicles in the cell body that
are transported to an axon terminal via fast axonal transport
 Synaptic terminal- smaller transmitters (acetylcholine, amines, purines) are made
in the synapse from enzymes from the cell body transported by slow axonal
transport

Transmitter Release
 Active zones/docking sites are on the presynaptic membrane; vesicles are located at
docking sites ready to release their transmitter
 Vesicles can be connected to the cytoskeleton by synapsin away from the docking site

Putting it Together – 1 AP releases 2-10 vesicles in the CNS (at NMJ around 120 vesicles are
released)
1. AP invades the presynaptic terminal
2. Depolarization of AP opens the voltage-gated Ca2+ channel in the presynaptic membrane
3. Ca2+ enters the presynaptic membrane by its electrochemical gradient
a. Large gradient, but not a lot of channels and low permeability (small current)
b. Ca2+ acts as a messenger rather than a depolarizing ion
4. Ca2+ entry causes
a. Some of the docked vesicles to release their transmitter into the synaptic cleft
i. To restore membrane, part of presynaptic membrane pinches off to form a
new vesicle that is refilled with transmitter in presynaptic terminal
b. Phosphorylates synapsins releasing the vesicles bound to the cytoskeleton
i. Vesicles migrate to open docking sites on the membrane, fusing with
presynaptic membrane
5. Released transmitter binds to postsynaptic receptor creating an interaction
a. Inotropic- transmitter binds directly to receptor channel and either opens or closes
the receptor channel
b. Metabotropic- transmitter binds to the receptor and receptor uses a second
messenger it signals another channel to open or close
6. If the transmitter is inotropic and opens the channel then ions flow through the open
channel
a. Current is dependent on channel selectivity and current direction depends on
electrochemical gradients
7. Acetylcholine is broken down by acetylcholinesterase (AChE) in the synaptic cleft
a. Acetate diffuses into ECF
 b. Choline is put back in presynaptic terminal by secondary active co-transport using
energy stored in Na+ gradient (Na+ goes down concentration gradient into the
cell and choline is transported with it)
i. Recycled choline combines with Acetyl CoA to make new acetylcholine
8. Acetylcholine stops binding to receptors and channels close
9. Postsynaptic potential decays and go back to resting potential due to K+ leakage channels

Transmitter Interaction
 Action on postsynaptic membrane may be excitatory (current that causes depolarization
above threshold) or inhibitory (currents that hyperpolarize below threshold), depending
on the ion
o Excitatory Postsynaptic Potentials (EPSP)- cause depolarization
 Channels open, increasing Na+ permeability, Na+ enters into the
postsynaptic cell through its electrochemical gradient causing
depolarization causing a postsynaptic AP
 One CNS EPSP is not enough to cause depolarization need multiple
(summation) to reach threshold
o Inhibitory Postsynaptic Potentials (IPSP)- cause hyperpolarization
 Happens in CNS and autonomic synapses NOT at NMJ
 Channels open, permeable to K+, K+ leaves postsynaptic cells and move
down its electrochemical gradient resulting in hyperpolarization and
making it more difficult for AP to occur because it is pulling the cell
farther away from threshold
 Increasing Cl- permeability will drag membrane potential away from
threshold toward Cl- resting potential resulting in an ISPS

Action Potentials vs. Synaptic Potentials

 Both change the membrane of the cell
 AP: produced by voltage-gated channels, all-or-none response, no summation,
depolarization activates another depolarization (propagate)
 Synaptic Potentials: non-electrical (non-voltage), produced by transmitter (ligand) gated
channels, amplitude depends on the amount of transmitter present and number of
channels that open, can be summed, do not propagate
o Postsynaptic Potential (PSP) causing postsynaptic excitability depends on the
amplitude (the amount of transmitter released) and can happen presynaptically or
postsynaptically
 More transmitter - more open postsynaptic channels – more postsynaptic
current – more current – bigger PSP – more influence on excitability

The distance from the axon hillock determines how influential the synapse is

Amount of Transmitter Released

 Summation: need multiple EPSPs to depolarize the cell to threshold
o Temporal: one synapse producing series of EPSPs
 No summation- transmitter released is degraded in cleft before the next
stimulus arrives
  Summation- rapid stimulation occurs and transmitter is not yet degraded to
the amount of transmitter can build up opening channels bringing the
postsynaptic membrane to threshold and producing an action potential
o Spatial: multiple synapses are excitatory producing EPSP
 No summation- each synapse produces subthreshold EPSP and there isn’t
enough transmitter in the cleft at a time to bring the postsynaptic cell to
threshold
 Summation- all synapses are stimulated simultaneously producing large
EPSP bringing postsynaptic cell to threshold and producing an action
potential
 Postsynaptic inhibition: if an inhibitory synapse fires, the hyperpolarizing current can
cancel some of the depolarizing current stopping the action potential
 Presynaptic Facilitation: increases the amount of transmitter released
o Synapse at presynaptic axon releases transmitter that can block voltage gated K+
channels from opening, which can lead to a longer AP – longer Ca2+ channels
open – more Ca2+ - more transmitter release – larger excitatory response
 Presynaptic Inhibition: decreases the amount of transmitter released
o Decreasing amount of Ca2+ inside – fewer vesicles released – less transmitter
released into cleft – fewer postsynaptic channels – less postsynaptic current –
smaller postsynaptic potentials (PSP) – decreased excitability on PSPx

Review
 An IPSP can be created by the increased permeability of the postsynaptic cell to K+ and
Cl-
 An EPSP will be created by an increase in Na+ permeability
 Properties of postsynaptic potentials- can add postsynaptic potentials to make it bigger or
smaller (summation)
 Property of an electrical synapse- connexons connect pre and post, physical continuity in
electrical synapse, direct spread of ionic current between the axoplasm of the pre and
postsynaptic cells
 CNS AP is initiated at the axon hillock
 Chemical synapses are most prevalent in the CNS