Download Synaptic transmission

SYNAPTIC
TRANSMISSION
2012
Yasemin Keskin-Ergen
Synapse
• The point where the two neurons communicate.
• The word comes from "synaptein", which Charles Scott
Sherrington and colleagues coined from the Greek "syn-"
("together") and "haptein" ("to clasp").
Spinal motor neuron - 10.000 contacts
- 2000 on its cell body
- 8000 on its dendrites
Purkinje cells ~150.000 contacts
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Kandel et al. Principles of Neural Science, McGraw Hill, 2000
Synaptic transmission
Electrical synapses Chemical synapses
Electrical synapses are formed by gap junctions that allow direct
passage of molecules between neurons, creating a cytoplasm-tocytoplasm connection
They are more common in the central nervous system than
previously thought.
Gap junctions are found between glial cells as well.
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Kandel et al. Principles of Neural Science, McGraw Hill, 2000
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Kandel et al. Principles of Neural Science, McGraw Hill, 2000
Electrical Transmission Allows the Rapid and Synchronous Firing of
Interconnected Cells
Electrical transmission is useful for connecting large groups of neurons.
Transmission across electrical synapses is extremely rapid because it results from the
direct flow of current from the presynaptic neuron to the postsynaptic cell. Since
current flows across the membranes of all electrically coupled cells at the same time,
several cells can act coordinately as one large cell.
Electrical synaptic transmission was first demonstrated at the giant motor synapse in the crayfish
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Kandel et al. Principles of Neural Science, McGraw Hill, 2000
Electrical transmission is graded and occurs even when the currents in the
presynaptic cell are below the threshold for an action potential.
Gap-junction channels are relatively large and nonselective, they allow passage of
large cation and anions, and compounds like chemical messengers (e.g., IP3, small
peptides) to flow through.
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Kandel et al. Principles of Neural Science, McGraw Hill, 2000
Distinguishing properties of electrical and chemical synapses
Type of synapse
Distance
between cell
membranes
Agent of
transmission
Synapitc
delay
Direction of
transmission
Electrical
3.5nm
Ion current
Virtually
absent
Usually
bidirectional
Chemical
20-40nm
Chemical
transmitter
At least 0.3ms
usually 1-5ms
Unidirectional
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Kandel et al. Principles of Neural Science, McGraw Hill, 2000
CHEMICAL SYNAPSES
Axosomatic synapse:
between axon
terminal of a neuron
(sender) and cell
body of a target cell
(receiver)
Axodendritic synapse: between axon terminal of a neuron (sender)
and dendrite of target cell (receiver)
InterActive Physiology 10-System Suite. (Cummings Publishing Company), 2006
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Ligand gated ion channels:
ACh: Acetylcholine
Ligand-gated ion channel receptors:
The channel opens with binding of a specific
neurotransmitter  ionic flow change in
mebrane potential of postsynaptic membrane
(postsynaptic potentials)
These channels are mostly
located on the dendrites and the
cell body (receptive portion)
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InterActive Physiology 10-System Suite. (Cummings Publishing Company), 2006
Neurotransmitters act either directly or indirectly on ion channels that regulate
current flow in neurons
Ionotropic receptor
Metabotropic receptor
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Kandel et al. Principles of Neural Science, McGraw Hill, 2000
1.AP reaches the presynaptic axon terminal and causes
the voltage gated Ca2+ channels to open
Ca2+
Neurotransmitter
vesicles
2. Presence of Ca2+ causes synaptic vesicles to fuse with
membrane.
3. Neurotransmitters stored in vesicles are released and
they diffuse across the synaptic cleft and bind to their
receptors over the postsynaptic membrane
4. These receptors change the membrane potential directly
or indirectly by changing the membrane permeability to the
specific ions
5. Based on the neurotransmitter and/or reecptor type
Depolarization
Hyperpolarization
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InterActive Physiology 10-System Suite. (Cummings Publishing Company), 2006
Excitatory postsynaptic potential (EPSP) depolarize neurons
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Kandel et al. Principles of Neural Science, McGraw Hill, 2000
The combination of excitatory and inhibitory
synaptic connections mediating the stretch
reflex of the quadriceps muscle is typical of
circuits in the central nervous system.
Neurotransmitter: glutamate
Channels: glutamate-gated
permeable to Na+.
Neurotransmitter: Glycine
Channels: ligand gated Clchannels
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Kandel et al. Principles of Neural Science, McGraw Hill, 2000
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Kandel et al. Principles of Neural Science, McGraw Hill, 2000
Synaptic potentials are graded potentials
Neurotransmitter release is directly related with the
Many EPSPs are needed to depolarize a neuron
amount of Ca2+ that enters the presynaptic terminal.
to the threshold.
When the amount of Ca 2+ entering the presynaptic
terminal is altered, the synaptic potential may be
enhanced, or weakened.
15
InterActive Physiology 10-System Suite. (Cummings Publishing Company), 2006
Temporal & Spatial summation
The EPSP produced by the one neuron often far below the threshold for generating an
action potential.
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INTEGRATION
• Many EPSPs are needed to depolarize
a neuron to the threshold.
• IPSPs cancel the effects of excitatory
activity and can prevent the
postsynaptic cell form generating an
action potential.
• The closer a synapse is to the trigger
zone, the greater the effectiveness of
that synapse.
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InterActive Physiology 10-System Suite. (Cummings Publishing Company), 2006
Signal Type
Amplitude Duration
(mV)
Summation
Effect of signal
Type of
propogation
-Synaptic potentials
0.1-10
5ms-20min
Graded
Hyperpolarizing/ Passive
Depolarizig
- Action potential
70-100
1-10ms
All-or-none
Depolarizing
Active
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Kandel et al. Principles of Neural Science, McGraw Hill, 2000
Neurotransmitter effects
The action of a transmitter in the postsynaptic cell does not only depend on the chemical
properties of the transmitter but rather on the properties of the receptors that recognize and
bind the transmitter.
Major neurotransmitters:
• Amino acids: glutamate, γ-aminobutyric acid (GABA), glycine
• Monoamines and other biogenic amines: dopamine (DA), norepinephrine (noradrenaline;
NE, NA), epinephrine (adrenaline), histamine, serotonin (SE, 5-HT)
• Peptides: somatostatin, opioid peptides
• Others: acetylcholine (ACh), adenosine, nitric oxide
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Glutamate receptors
• Ionotropic
(named according to the types of synthetic agonists that activate them)
– AMPA (a-amino-3-hydroxy-5-methylisoxazole-4-propionic acid*)
– Kainate
– NMDA (N-methyl-D-aspartate)
• Metabotropic
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Kandel et al. Principles of Neural Science, McGraw Hill, 2000
Glutamate receptors
Non-NMDA ionotropic receptors generate the
large early component of the EPSP in most of
the neurons. These receptors are permeable to
both Na+ and K+ but are usually not
permeable to Ca.
The NMDA receptor-channel contributes to the late component
of the EPSP.
- NMDA receptor is permeable to Ca2+ as well as to Na+ and K +.
- opening depends on membrane voltage as well as a chemical
transmitter.
When the membrane is depolarized Mg 2+ is expelled from the channel by electrostatic
repulsion, allowing Na + and Ca2+ to enter.
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Kandel et al. Principles of Neural Science, McGraw Hill, 2000
GABA Receptors
• Gamma-aminobutyric acid (GABA) is a major
inhibitory transmitter in the brain and spinal
cord.
• It acts on two receptors: GABAA and GABAB.
• The GABAA receptor is an ionotropic receptor
that gates a Cl - channel.
• The GABAB receptor is a metabotropic
receptor that activates a second-messenger
cascade, which often activates a K + channel.
GABAA Receptor
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Termination of Synaptic Transmission
Neurotransmitters
dissociate from
receptors
Neurotransmitters must be
reabsorbed or broken down once it
reaches the synaptic cleft to
prevent further excitatory or
inhibitory signal transduction.
Pumped into the
presynaptic terminal
Broken down by the
enzymes
Breakdown products
are taken up by the
presynaptic cell
e.g., ACh is broken down
by acetylcholinesterase (AChE).
Choline is taken up and recycled by
the pre-synaptic neuron to
synthesize more ACh.
Neurotransmitter
resyntesized
Neurotransmitters
repacked into
vesicles
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Drug Action on Neurotransmission
Many important psychopharmacological agents target:
-Neurotransmitter receptors
- Enzymes that regulate neurotransmitter synthesis or degradation
- Neurotransmitter re-uptakers.
Agonists of a neurotransmitter binds to its receptor and mimicks the endogenous
neurotransmitter (e.g. A full agonist open the ion channel)
Antagonist binds to receptor but stabilizes the channel in resting state (release of few
ions).
Resting state
Full agonist opens the channels
Antagonist stabilizes the
channel in resting state
Drug Action on Neurotransmission
Positive allosteric modulation: potentiation of the channel by a substance
other than the neurotransmitter.. (another binding site)
NT1: Neurotransmitter
PAM: Positive allosteric modulator
Drug Action on Neurotransmission
Negative allosteric modulation: The drug binds to the channel and blocks
the channel reduce the effects of the neurotransmitter..
NT1: neurotransmitter
NAM : negative allosteric modulator
Drug Action on Neurotransmission
Drugs can promote or inhibit the activity of presynaptic re-uptaker of the nerotransmitter
(e.g. A re-uptake blocker would let a neurotransmitter to act on postsynaptic receptor for a
longer period  enhanced chemical signalling)