SYNAPTIC TRANSMISSION & PLASTICITY Flashcards
Synapse
– Connection between two neurons
(– Commonly, the axon of a pre-synaptic neuron contacts the dendrite of a post-synaptic neuron)
Neurotransmitter
Chemical messenger sent across synapse, from pre-synaptic neuron to post-synaptic neuron
Receptor
– Protein in cell membrane to which neurotransmitters bind
(– Commonly, a receptor is a ligand-gated ion channel, where the ligand is a neurotransmitter)
Post-synaptic potential
– Subthreshold change in cell membrane potential due to movement of ions through channels
(– Post-synaptic potentials can be excitatory or inhibitory)
Synaptic plasticity
– Change in how effectively information is transmitted across a synapse
(– Change in magnitude of the post-synaptic potential elicited by a pre-synaptic action potential)
Axo-dendritic synapse
likely the most common type
Axo-somatic synapse
can have relatively large influence on action potential generation from post-synaptic cell
Axo-axonic synapse
can influence transmitter release from post-synaptic cell
Synaptic cleft
space between pre-synaptic neuron and post-synaptic neuron
about 20nm wide (20 x 10-9m)
Amino Acids
Main inhibitory transmitter in cerebral cortex
GABA, Glu (excitatory in cerebral cortex), Gly
Amines
Commonly act as neuromodulators in brain, i.e., modulate influence of amino acid transmitters
Neurotransmitter release
1) Synaptic vesicle docked at pre-synaptic “active zone”
2) Action potential leads to increased pre-synaptic calcium
3) Calcium triggers neurotransmitter release
4) Synaptic vesicle recycled
Calcium triggers vesicle fusion with cell membrane
Proteins dock vesicle to cell membrane:
– SNARE proteins mediate fusion
– (SNARE = soluble NSF attachment receptor)
– Synaptotagmin activates fusion proteins
Calcium (Ca2+) binds to synaptotagmin
– Synaptotagmin acts as calcium sensor
– Synaptotagmin triggers fusion and transmitter release
ligand-gated ion channel
Transmitter-gated ion channel
Transmitters bind to particular sites on channels:
– Transmitter-gated ion channels also called “receptors”
Transmitter-gated ion channel contains two functional domains:
– Extracellular domain contains neurotransmitter binding sites
– Membrane-spanning domain forms the ion channel
Transmitter binding leads to channel opening and membrane potential change:
– Positive ions (Na+, Ca2+) into cell causes depolarization (membrane potential more positive)
– Negative ions (Cl-) into cell causes hyperpolarization (membrane potential more negative)
Transmitter-gated ion channels produce rapid post-synaptic effects:
faster effects than G-protein-coupled receptors
Receptor Subtypes
AMPA receptor = ionotropic
NMDA receptor = ionotropic (transmitter-gated and voltage-gated)
GABA A receptor = ionotropic
GABA B receptor = metabotropic
Synaptic plasticity
change in synaptic strength
– Change in how effectively information is transmitted across a synapse
– Change in magnitude of post-synaptic potential (PSP) elicited by pre-synaptic action potential
Synaptic strength can be increased or decreased
– Increased synaptic strength facilitates (potentiates) synaptic transmission (increased PSP)
– Decreased synaptic strength depresses synaptic transmission (decreased PSP)
Short-term synaptic plasticity
– Short-term synaptic plasticity, lasting tens-to-thousands of milliseconds
– Short-term facilitation and short-term depression are temporary changes in synaptic strength
– Without continued pre-synaptic activity, synaptic strength will return to baseline level
Long-term synaptic plasticity
– Long-term synaptic plasticity, lasting minutes-to-hours and more
– Long-term potentiation and long-term depression
– Considered to be important mechanism underlying learning and memory
Long-term potentiation (LTP)
LTP is increased EPSP of post-synaptic neuron in response to pre-synaptic input
High-frequency activity (e.g., 100Hz for 1s) of pre-synaptic cell can induce LTP
LTP is input-specific – Increased EPSP only at synapses where pre-synaptic neuron was active
Large increase in Ca2+ inside post-synaptic cell induces LTP
Mechanisms for long-term potentiation (LTP)
1) Increase effectiveness of AMPA receptor:
– i.e., phosphorylate AMPA receptor (add P043-):
2) Insert more AMPA receptors into synapse:
– Neurotransmitter can bind more receptors
3) Increase neurotransmitter release:
– Retrograde messenger (e.g., nitric oxide) sent from post-synaptic cell to pre-synaptic cell
– This increases pre-synaptic Ca2+ and transmitter release
Long-term depression (LTD)
LTD is decreased EPSP of post-synaptic neuron in response to pre-synaptic input
Low-frequency activity (e.g., 1Hz for 10min) of pre-synaptic cell can induce LTD
LTD is input-specific – Decreased EPSP only at synapses where pre-synaptic neuron has low activity
Small increase in Ca2+ inside post-synaptic cell induces LTD
Two types of post-synaptic potentials
– Excitatory post-synaptic potential (EPSP) produced by glutamate
– Inhibitory post-synaptic potential (IPSP) produced by GABA