Title: Synaptic Transmission
1Synaptic Transmission
- Synapse specialized junction where an axon
terminal contacts another neuron or cell type - Types of synapses
- Electrical synapses
- Chemical synapses
- An understanding of synaptic transmission is
necessary to understand the operations of the
nervous system (ie. actions of psychoactive
drugs, causes of mental disorders, neural basis
of learning and memory)
2Electrical Synapses
- Allows the direct transfer of ionic current from
one cell to the next. - Gap Junction is composed of 6 connexins that
make up a connexon. (Pore size 2nm) - Ions can flow bidirectionally.
- Cells are electronically coupled.
- Conduction speed is very fast.
- Found in neuronal pathways associated with
escape reflexes or in neurons that need to be
synchronized. - Common in non neuronal cells.
- Important in development
3Chemical Synapses
- Synaptic cleft
- 20 50 nm wide
- Held together by a fibrous extracellular matrix
- Synaptic bouton (presynaptic element)
- Contains synaptic vesicles (50nm in diameter)
and secretory granules (100 nm) called large,
dense core vesicles. - Membrane differentiations accumulations of
proteins on either side of the synaptic cleft - Active zones presynaptic site of
neurotransmitter release - Postsynaptic density contains receptors to
translate intercellular signal (neurotranmitter)
into an intracellular signal (chemical change or
membrane potential change)
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6Synapses can be categorized by
- Connectivity which part of the neuron is
postsynaptic to the axon terminal - Synapse anatomy
- Size and shape
- Appearance of the pre and postsynaptic membrane
differentiations. - Grays type I synapses asymmetrical
(postsynaptic membrane is thick) - Grays type II synapses - symmetrical
7CNS Synapses types of connections
Axodendritic
Axosomatic
Axoaxonic
8Synapses differentiated by size and shape.
9Categories of CNS membrane differentiations.
Grays type I synapses
Grays type II synapses
Usually Excitatory
Usually Inhibitory
10- Synaptic Junctions Exist Outside the Brain
- Junctions between autonomic neurons and glands,
smooth muscle, and heart. - The Neuromuscular Junction
- Transmission is fast and reliable due to large
size with many active zones and a motor end plate
with specialized folds for more receptors.
11Requirements of Chemical Synaptic Transmission.
- Mechanism for synthesizing and packing
neurotransmitter into vesicles. - Mechanism for causing vesicle to spill contents
into synaptic cleft in response to action
potential. - Mechanism for producing an electrical or
biochemical response to neurotransmitter in
postsynaptic neuron. - Mechanism for removing transmitter from synaptic
cleft. - Must be carried out very rapidly.
12Neurotransmitters
- Amino Acids
- synaptic vessicles
- Amines
- synaptic vessicles
- Peptides
- secretory granules.
- Peptides may exist in the same axon terminals as
amino acids and amines. - Fast transmission uses Amino acids or ACh.
- Slow transmission may use any of the three types
of neurotransmitters
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14Neurotransmitter Synthesis and Storage
Synthesis of peptide neurotransmitters
Synthesis of amine and amino acids
15Neurotransmitter Release
- Action potential enters the axon terminal.
- Voltage gated Ca channels open.
- Ca activates proteins in the vesicle and active
zone. - Activated proteins causes synaptic vesicles to
fuse with membrane. - Neurotransmitter is released via exocytosis.
- Note Peptide release requires high frequency
action potentials and is slower (50 msec vs. 0.2
msec).
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18Neurotransmitter Receptors and Effectors
- Neurotransmitters must bind to specific receptor
proteins in the postsynaptic membrane. - Binding causes a conformational change in the
receptor. - A change in structure equals a change in
function. - Over 100 different types of receptors.
- Two major categories of receptors
- Transmitter (ligand) gated ion channels.
- G-protein coupled receptors.
19Ligand-gated Ion Channels
- Structure Channel protein with a ligand binding
domain. - Neurotransmitter binding causes channel to open.
- Consequence depends on the specific ions that
pass through the pore. - Na and K channels cause depolarization and are
excitatory. - Cl- channels cause hyperpolarization and are
inhibitory. - Activation is generally rapid and is mediated by
amino acids and amines.
20Excitatory Postsynaptic Potential (EPSP)
Excitatory Neurotransmitters ACh and glutamate
21Inhibitory Postsynaptic Potential (IPSP)
Inhibitory Neurotransmitters Glycine and GABA
22G Protein-Coupled Receptors
- Structure Receptor protein with a ligand binding
domain and connected to G protein consisting of
an alpha, beta and gama subunit. - Activation 1) Ligand binds to receptor 2)
Receptor activates G-protein 3) G-protein
dissociated 4) alpha subunit activates an
effector protein. - Effectors G-proteins act in one of two ways
- By opening ion channels
- By activating enzymes that synthesize
second-messenger molecules. - Tend to be slower, longer lasting and have
greater diversity than ligand gated ion channels. - Ligand may bind to a family of receptors with
different effects due to specific receptor type.
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24Autoreceptors and Presynaptic Inhibition
- Receptors are sometimes found on the presynaptic
terminal. - Activation leads to
- Inhibition of neurotransmitter release
- Neurotransmitter synthesis.
- Autoreceptors may act as a brake on the release
of neurotransmitters.
25Neurotransmitter Recovery and Degradation
- Neurotransmitters must be cleared from the
synapse to permit another round of synaptic
transmission. - Methods
- Diffusion
- Enzymatic degradation in the synapse.
- Presynaptic reuptake followed by degradation or
recycling. - Uptake by glia
- Uptake by the postsynaptic neuron and
desensitization.
26Neuropharmacology
- Synaptic transmission is a chemical process and
therefore can be affected by drugs and toxins. - Neuropharmacology is the study of the effects of
drugs on the nervous system - Receptor Antagonists inhibit the normal action
of a neurotransmitter. - Curare blocks the action of ACh at the
neuromuscular junction. - Receptor Agonists mimic the action of a
neurotransmitter. - Morphine activates Mu-opiate receptors in the
brain. - Nervous system malfunctions are often related to
neurotransmission errors.
27Synaptic Integration
- Each neuron may receive thousands of inputs in
the form of ion channel and G-coupled protein
activation. - These complex inputs give rise to simple output
in the form of action potentials. - Neural computation
- Neurotransmitters are released in quanta.
- EPSP Summation
- Neurons do sophisticated computations by adding
together EPSPs to produce a significant
postsynaptic depolarization. - Types of Summation Spatial and Temporal
Summation.
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29Dendritic Cable Properties
-Triggering of an action potential depends on how
far the synapse is from the spike initiation zone
and the properties of the dendrite (ie. Internal
and membrane resistance.) -Some dendrites have
voltage gated channels that can help amplify
signals along dendrites.
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31Inhibition
IPSP are generated when ion channels are opened
causing hyperpolarization of the membrane. Ie.
GABA or glycine opens Cl- channels Shunting
Inhibition inward movement of Cl- anions will
negate the flow of positive ions.
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