Synaptic 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)
Electrical 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
Chemical 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)
Synapses can be categorized by:
1. Connectivity – which part of the neuron is
postsynaptic to the axon terminal
2. Synapse anatomy
–
–
Size and shape
Appearance of the pre and postsynaptic
membrane differentiations.
•
•
Gray’s type I synapses – asymmetrical
(postsynaptic membrane is thick)
Gray’s type II synapses - symmetrical
CNS Synapses – types of connections
Axodendritic
Axosomatic
Axoaxonic
Synapses differentiated by size and shape.
Categories of CNS membrane differentiations.
Gray’s type I synapses
Usually Excitatory
Gray’s type II synapses
Usually Inhibitory
•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.
Requirements of Chemical
Synaptic Transmission.
1. Mechanism for synthesizing and packing
neurotransmitter into vesicles.
2. Mechanism for causing vesicle to spill contents
into synaptic cleft in response to action potential.
3. Mechanism for producing an electrical or
biochemical response to neurotransmitter in
postsynaptic neuron.
4. Mechanism for removing transmitter from
synaptic cleft.
5. Must be carried out very rapidly.
Neurotransmitters
1. Amino Acids
–synaptic vessicles
2. Amines
–synaptic vessicles
3. 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
Neurotransmitter Synthesis and Storage
Synthesis of peptide
neurotransmitters
Synthesis of amine
and amino acids
Neurotransmitter Release
1. Action potential enters the
axon terminal.
2. Voltage gated Ca++
channels open.
3. Ca++ activates proteins in
the vesicle and active
zone.
4. Activated proteins causes
synaptic vesicles to fuse
with membrane.
5. Neurotransmitter is
released via exocytosis.
Note: Peptide release requires
high frequency action
potentials and is slower
(50 msec vs. 0.2 msec).
Neurotransmitter 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.
Ligand-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.
Excitatory Postsynaptic Potential (EPSP)
Excitatory Neurotransmitters:
ACh and glutamate
Inhibitory Postsynaptic Potential (IPSP)
Inhibitory Neurotransmitters:
Glycine and GABA
G 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 secondmessenger 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.
Autoreceptors 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.
Neurotransmitter 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.
Neuropharmacology
• 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.
Synaptic 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.
Dendritic 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.
Inhibition
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.