CSB332H1S L11; Feb. 15, 2012 Key w synaptic plasticity:
Synaptic Plasticity o Change in synapse strength persists after activity (ex. train of
Read Ch. 16 APs) that induced plasticity
Changes in presynaptic &/or postsynaptic [Ca2+]i underlie most
Plasticity is the capacity of the nervous system to change forms of synaptic plasticity
Today talking about short-term o ex. phosphorylates AMPA recs
Synaptic plasticity = the capacity to alter the strength of synaptic Mechanisms often classified as presynaptic or postsynaptic
transmission Long-term potentiation = most-studied form of synaptic plasticity
o Modifying connections
o Short-term (ms - mins, don’t normally require prot synthesis) or
long-term (hrs, need prots to maintain long-term, GABA)
o Can be due to Presynaptic &/or Postsynaptic changes
Most short-term due to Presynaptic
Most long-term need Postsynaptic (need retrograde
signalling)
Always changes on both sides of synapse
o = a change in synaptic efficacy or strength
Efficiency of transmission
Hebbian (Activity-dependent)
o Talking about most
o Plasticity induced by pattern of electrical activity (act pot firing)
o Hebb = name of famous Canadian neuropsychologist
or Heterosynaptic (Activity-independent)
o chemical LTP, using some kind of ligand, without changing
pattern of act pot firing
How can we test for synaptic plasticity?
Mostly looking at neuromuscular junction
To test strength of synapse:
o Stimulating electrode placed in presynaptic cell or bundle of
axons & Recording electrode placed in postsynaptic cell or
muscle
Stimulation of presynaptic cell firing of a presynaptic AP & release
of neurotransmitter
Binding of neurotransmitter postsynaptically opens ion channels
(ionotropic or metabotropic) synaptic pot – recorded
postsynaptically
Amplitude of synaptic pot recorded postsynaptically is a measure of Short-term
Looking at amplitudes in postsynaptic muscle
strength of synapse Can induce two types of plasticity at same synapse
o Using test pulse/stimulation first Mech is Ca
o First use low freq (Hz) to stimulate 1 act pot (don’t usually
activate synapse or induce plasticity on own) In general, most synapses are more likely to either be facilitated or
1 Hz = 1 stimulation per second (1 act pot) depressed
o Test for 10min to make sure have steady baseline Stimulate 4 times produces 4 end-plate pots of dif sizes
o increase = facilitation
Initial baseline-recording period o Wait a couple ms stimulation second end-plate pot = larger
o Once confident in baseline, induce plasticity (Induction
Protocol) than initially was, but not as large as biggest
Then test synapse again like in baseline test, see if changed Artificially regulating level of extracellular Ca
strength (amplitude changes), compare to baseline o Short term mechs are dependent on amt of Ca, so trying to
See if change persists after induction exaggerate to illustrate pt
Bathed tissue in lower level of extracellular Ca
o mech underlying facilitation partially due to amt of Ca in
presynaptic synaptic terminal
Time for chelation & for levels to rise again
Ca levels normally build more neurotransmitter
released
So 3ms later, end-plate pot larger
But 1 sec later, response gone
o At NMJ, firing 1 act pot can often cause a postsynaptic act pot,
Stimulating electrode in bundle of presynaptic axons in hippocampus but want to measure underlying end-plate pots end-plate
pots smaller
Recording electrode on dendrites in CA1 region Effect outlasts initial induction stimulus but lasts shortly for only a
Synaptic Plasticity second
Arrival of indiv APs presynaptically don’t usually activate synapse B: bath synapse in high level of Ca
Trains of APs are more common o Also puts curare in bath (antagonist of Ach) lowers synaptic
response
Such ongoing activity can have significant effects of strength of o Mech depends on amt of Ca
synapse o depression
Changes in synapse strength = changes in synaptic efficacy
When activity (trains or patterns of APs) cause change in synaptic o Release a lot of quanta but subsequent atc pots are smaller
efficacy: Ca comes in, nearly all vesicles released so that less
available to be released at 2 act pot
o Activity-dependent synaptic plasticity Rapidly depleted synaptic vesicles o If were to stimulate again, would see end-plate pot at 300ms o Hard to measure underlying amplitude of end-plate pots, want
would still be smaller (outlasts stimulus), but back to normal to weaken by hyperpolarizing membrane pot so at more
after 1 sec (enough time to move vesicles from reserve pool to negative value further from threshold more unlikely to reach
terminal) for act pot
o Ca levels usually constant in cerebrospinal fluid o Stimulate synapse record wave form w two parts
Depends on microdomains & other factors regulating Initial peak than secondary peak
neurotransmitter release Initial peak doesn’t change in amplitude
C: combine A & B Indicates there is an electrical synapse, not chemical;
o Get some elements of fac & depr occurring together also know since see response immediately
o Get fac but then 3 & 4 are same Secondary wave form = end-plate pot
o At 300ms, test synapse, response much smaller so synapse has o Test strength of synapse (control)
undergone a depression o Induction protocol then see if plasticity occurs
So need to test synapse after the Induction Protocol and T=0
compare to initial test Don’t care what it looks like during induction
o 15s after, test strength huge end-plate pot that leads to act
pot; so know there has been huge increase in synapse strength;
end-plate pot was 1mV before
o Wait 1min, test again see huge end-plate pot but not enough
to reach threshold
o By 10min, returns close to baseline but still larger, so know isn’t
long-term form of
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