BIO 448 - Synaptic plasticity

synaptic plasticity

change in synapses over time that can either weaken or strengthen synaptic transmission

short term plasticity

• facilitation

• augmentation

• depression

• potentiation

synaptic facilitation

rapid increase in synaptic strength that occurs when 2 or more action potentials invade the presynaptic terminal within a few milliseconds

• same stimulus but better response in postsynaptic cell

• neurotransmitters haven’t cleared when second action potential comes in, so you release more vesicles the second time because of increased calcium levels

• could be due to more occupancy of synaptotagmin by calcium

disappear when interval between action potential is increased

synaptic depression

NT release declines during sustained synaptic activity

due to depleted pool of presynaptic docked vesicles despite presence of action potential

slower rate of depression = lower levels of calcium

the more NT released the more synaptic depression observed

seconds scale

synaptic augmentation

NT release increases during sustained synaptic activity

due to enhanced ability of incoming calcium ions to trigger fusion of synaptic vesicles with the plasma membrane

effects last seconds

could be presynaptic second messengers that increase likelihood that synaptic vesicles will fuse with membrane in response to calcium influx

might involve munc-13 which is a calcium effector protein binding to calcium and thus when additional calcium builds up it binds to accessory proteins as well with interact with SNAREs to make fusion to membrane more efficient

synaptic potentiation

also called post-tetanic ___

effects last minutes

due to prolonged activity of presynaptic calcium levels which may regulate protein kinases that phosphorylate substrates which themselves regulate NT release

enhanced response after stimulus

concurrent

all short-term synaptic plasticity mechanisms are ___

order of events

• facilitation = presynaptic accumulation of Ca2+

• augmentation = presynaptic accumulation of Ca2+ & activation of short-lived Ca2+ dependent second messenger

• depression = high frequency stimulation causes short-term depletion of releasable pool of synaptic vesicles aka docked vesicles

• potentiation = high frequency stimulation causes activation of second messenger system aka kinases which results in increased NT release

presynaptic terminal

for short-term synaptic plasticity, all mechanisms happen in the ___

hippocampus

learning and memory mainly happens in the ___

neurons in a granule cell from the dentate gyrus region connects to a CA3 pyramidal cell neuron via mossy fibers, and that neuron connects to CA1 pyramidal cell neuron.

Long term potentiation (LTP)

when 2 neurons connect to the same dendrite, tetanus stimulus on one neuron does NOT affect the other one despite their common target

lasts for hours/days/years

capable of serving as a mechanism for long-lasting storage of information aka cellular mechanism for memory

properties of LTP

• specificity

• associativity

specificity

LTP is induced by activation at one synapse

it does not occur in another INACTIVE synapse aka the cell needs to already be depolarized for it to work

associativity

if one pathway is weakly activated at the same time as another pathway is activated, then BOTH strong and weak undergo LTP

since most charge will transfer from the synapse to the dendrite, strong activation of a synapse can help boost the effects of a weak neighboring synapse

LTP mechanism

during postsynaptic depolarization, NMDA receptor is booting off the magnesium and thus allow calcium to come into the cell which in turn triggers LTP

BOTH

__ presynaptic and postsynaptic neurons must be active (depolarized) to get LTP

induction

__ of LTP is associated with increase in local Ca2+

result

one of the ___ of LTP is increased sensitivity to glutamate

AMPA

Increased Postsynaptic response to glutamate is due to insertion of extra ___receptors into the membrane

in response to calcium going through the NMDA receptor and binding to endosome ___ receptors, it is causing part of the endosome to detach and fuse with postsynaptic membrane.

This increases the number of postsynaptic __ receptors

events leading to LTP

1. NMDA channels open if sufficiently depolarized

2. calcium influx

3. activation of protein kinases

4. insertion of new AMPA receptors

5. sensitivity to glutamate

6. LTP

This explains the short-term LTP which is on the scale of hours. Another mechanisms but exist for it to last years.

gene expression

long long-term LTP is due to the influx of calcium activating kinases and second messengers which alter gene expression and makes new proteins

protein synthesis

you need new ___ for long term LTP maintenance which stands from changes in synaptic architecture