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Transcript
Lecture outline of synaptic transmission
SYNAPSE
Definition : Electrical signals must pass across the specialized gap region between two opposing cell
membranes called synapse.
SYNAPTIC TRANSMISSION:
The process underlying this cell-to- cell transfer of electrical signals.
Classification of Synapse:
A. Anatomical
1. Between 2 neuron (Neuro-neuro junction )
a. Axosomatic synapse
b. Axodenteritic synapse
c. Axoaxonic synapse
d. Axo-axonic & axodentritic
2. Between neuron & muscle Fiber (Neuromuscular junction)
B. Functional
Depending upon the basis of transmission of impulses
1. Electrical synapse
2. Chemical synapse
3. Conjoiny (both chemical & electrical)
•
Synaptic transmission can be classified in at least three ways:
1) Mechanism of transmission
Electrical transmission- direct flow of ions from one neuron to another, hence direct
influence of electric current from one to another
Chemical transmission- neurotransmitter substance released from presynaptic cell,
diffuses across synaptic cleft, produced effect on postsynaptic neuron
2) Whether it promotes or suppresses an active electrical response by postsynaptic neuron
Excitatory transmission- causes depolarization of postsynaptic neuron, in spiking
neurons increases probability of AP, in non-spiking neurons, increases amount of
neurotransmitter released
Inhibitory transmission- transmission which usually causes hyperpolarization of postsynaptic neuron, decreases probability of AP, in non-spiking neurons decreases
neurotransmitter release
3) Whether message is rapidly passed or whether characteristics of postsynaptic cell
modulated
Classical neurotransmission- signal is rapidly passed to postsynaptic cell, mediated by
ionotrophic receptors, mediate rapid electrical response of postsynaptic cell
Neuromodulatory transmission- characteristics of postsynaptic cell modulated, mediated
by metabotrophic receptors, which initiate biochemical cascade within the postsynaptic
neuron
Chemical synapse
• The transmitter at a chemical synapse can activate either an ionotropic receptor that is itself a
channel or a metabotropic receptor that is linked to a G protein.
• Ionotropic Receptors are nicotonic ACh receptors and lead to depolarization and action potential
excitation resulting in muscle contraction in skeletal muscle
Metabotropic receptors are muscarinic ACh receptors which activates release of α GTP+ßý from the
heterotrimeric G protein leads to activation of inward K+ channel by ßy eventually memb
hyperpolarization and decrease heart rate in cardiac muscle
Steps in Chemical Transmission
• STEP 1: neurotransmitter are packaged in synaptic vesicles.
• STEP 2: an action potential arrives at the preynaptic terminal.
• STEP 3:voltage- gated Ca channels open.Ca enters.
• STEP 4 :A rise in Ca triggers fusion of synaptic vesicles with presynaptic memb.
• STEP 5: Transmitter molecules diffuse across the synaptic cleft and bind to specific receptors on
the postsynaptic cell.
• STEP 6:Bound receptors activates the post synaptic cell.
• STEP 7 :A neurotransmitter breaks down,is taken up by the presynatic or diffuses away from the
synapse
Neurotransmitters
• AMINOACIDS-Gamma-amino butyric acid (GABA), Glutamate (Glu), Glycine (Gly)
• Amines; Acetylcholine (ACh), Dopamine (DA), Epinephrine, Histamine, Norepinephrine (NE),
Serotonin (5-HT)
• Peptides; Cholecystokinin (CCK), Dynorphin, Enkephalins (Enk), Neuropeptide Y, Somatostatin,
substance P, Thyroid releasing hormone, Vasoactive intestinal vasopeptide etc.
Excitatory Neurotransmitters:
• Glutamate – excitatory;
– binds to AMPA ionotropic receptors, which open Na+ channels
– binds to mGluR metabotropic receptors.
– binds to NMDA receptors, which can be both ionotropic and metabotropic because they
allow both Na+ and Ca+ to enter the neuron.
•
Acetylcholine – excitatory;
– binds to nicotinic ionotropic receptors, which open Na+ channels
– muscarinic metabotropic receptors
Inhibitory Neurotransmitters:
• GABA – inhibitory
– binds to GABA-A ionotropic receptors, which open Cl- channels
– Binds to GABA-B metabotropic receptor
•
Glycine – inhibitory;
– binds to ionotropic receptors, which open Cl- channels
Glutamate-amino acids
• Is a Neurotransmitter of excitatory synapses in majority in CNS.
• It is a precursor to GABA which is a major inhibitory NT.
• Glutamate has 4 major classes
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•
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G –protein linked metabotropic receptors
3-ionotropic receptors which are AMPA, NMDA and kainate
AMPA- amino methyl propionic acid –gated channels found in most excitatory synapses in
brain.GluR1-GluR4
NMDA-N- methyl D aspartate-gated channels .they allow entry of ca++ and have slower kinetics
because Mg++ blocks the NMDA receptors and when larger depolarization occur Mg++ detaches
and opens channel
Different from AMPA that both glutamate and glycine bind to open.
Other EPSP depolarize memb &Ca++ permeability---- hyperpolarization this lead to hypothesis
of role of learning & memory.
The ionotropic and metabotropic bind to glutamate but have evolved from diff ancestral protein
lines.
KAINATE receptors are present at the presynaptic GABAergic terminals and has inhibitory
control over GABA transmitter
Inhibitory Neurotransmitters/Receptors:
• GABA-----brain
• Glycine-----spinal cord
• They are ionotropic receptors
• Open Cl- channel
• GABA-A is ionotropic receptor
• It opens Cl- channels
• GABA-B receptor is metabotropic
• Binding of GABA activates GTP binding protein & activation K+ channel &hyperpolarization.
Turning Synapses Off
• Reuptake. NT is taken back into the synaptic knob of the presynaptic neuron actively. All NTs
except acetylcholine use this method.
•
Acetylcholine ; enzymatic breakdown into inactive fragments (acetylcholinesterase).
•
Nerve gases used in warfare (e.g., sarin) and the organophosphate insecticides (e.g., parathion)
achieve their effects by inhibiting acetylcholinesterase thus allowing ACh to remain active.
Atropine is used as an antidote because it blocks ACh receptors.
•
Spatial summation:
Refers to the fact that synapse potential generated at soma and dendrite interact leading
to a linear summation.
Temporal Summation:
The combined amplitude to reach threshold and lead to spiking of cell is called temporal
summation or can also occur when same synapse is activated multiple times lead to summation.
Neuromuscular transmission:
AP at motor nerve terminal → Ach release, across synaptic cleft → Ach + Nicotinic receptor → gNa+ >
 gK+ depolarization → EPP > Threshold → Muscle AP → Propagation of AP along sarcolemma
+T-tubule (local current propagation) → Muscle contraction
Presynaptic inhibition and excitation
Feed forward excitation and inhibition
Reverberating circuit
Disinhibition
Recurrent inhibition
Lateral inhibition
Learning objectives
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Synapse and its classification
Types of synaptic transmission
Steps involved in chemical transmission
Neurotransmitters and its types
Summation and its types
Neuromuscular transmission and its types