Synaptic Plasticity Flashcards
What is synaptic plasticity?
Refers to increases or decreases in synaptic strength in reponse to patterns of synaptic activity
What is synaptic facillitation?
Pheomenon in which postsynaptic potentials evoked by an impulse are increased when that impulse closely follows a prior impulse It is known as short term plasticity
What is synaptic depression?
When a train of stimuli being applied and the responses are decreasing in magnitude with time
Caused by depleting the pool of synaptic vesicles, so there’s mechanisms for recycling of these and with a train of stimuli then you may just be depleting that pool, so with time you end up getting shorter responses
Why is synaptic plasticity important?
Because it is thought to be the basis of learning and memory
What is the trisynaptic circuit of the hippocampus?
Inputs coming along this perforant path coming from the entorhinal cortex, these synapse on the dendrites of dentate gyrus neurons, dentate gyrus neurons in term send projections which synapse on cells in the CA3 regions and then these send axons which form these bundles called Schaffer collaterals and then these synapse on dendrites of neurons in the CA1 field and then those projections go back out to the entorhinal cortex
What are the basic properties of LTP (long term potentiation)?
Its cooperative- so you need a certain number of fibres to be stimulated, you’ve got to have a strong enough input, if you just get a weak input and record before and after you get the same response but this strong input is able to induce LTP so you get a bigger response after a strong input has been applied
Its input specific- so if you’ve got two inputs, one that is inactive and one that is active then with the strong bursts being applied to the active one you will observe LTP but something in the same pathway which wasn’t active when the high frequency burst was applied, you wont generate LTP there, so its input specific, it will only occur at active synapses
Its associative- get induction at concurrently active synapses- occurs when we have strong and weak, in this case we will induce LTP at the one receiving weak input because it was active at the time at which the high frequency burst was applied to the neuron
Hebb’s law- simplified to neurons that wire together fire together, about this idea of spike-timing dependent plasticity, so if you get stimulation of a presynaptic neuron which leads to activity in the post synaptic neuron, so occurs in the correct order then you strengthen those connections
What are the mechanisms underlying LTP?
Involves AMPA and NMDA receptors
AMPA receptors are important as they are the main current carrying glutamate receptors in normal excitatory transmission
But the induction of LTP also requires activation of NMDA receptors so if you block NMDA receptors then you block induction of LTP
How do AMPA receptors increase synaptic strength in LTP?
An increase in the number of AMPA receptors in the synapse causes depolarisation but there is also alleviation of the magnesium block so allowing calcium influx, then the calcium activates certain kinases, in particular, a class called calcium calmodulin dependent kinases and those will, through downstream mechanisms, lead to the insertion of additional AMPA receptors in the post synaptic membrane so now this post synaptic membrane has the ability to pass more current because there are more AMPA receptors there
What can increased AMPA activity cause?
Physical changes to the cytoskeleton and also to dendritic spines
e.g. research showed that increased glutamte concentration causes dendritic spines to get bigger in a matter of minutes and they remain bigger in size
Also in arease where there were no spines, new spines were generated
What has CREB go to do with LTP?
Essentially it is the late phase of LTP
Part of the LTP response is changes in gene expression e.g. CREB
Activation of NMDA receptors and alleviation of the magnesium block will lead to calcium and we’ve got calcium sensitive kinases being activated, so calcium calmodulin kinase II and that activates other signalling pathways which culminate with the phosphorylation of CREB and changes in gene expression
What is the difference between LTP and LTD?
LTD also invovles the internalisation of AMPA but induction of LTD is sensitive to phosphatase inhibitors (rather than kinases in LTP) where activation of phosphatase casues the removal of phosphates e.g. stargazin and this dephosphorylation will cause the removal of AMPA receptors from synapses
What causes LTD in the cerebellum?
The paired stimulation of climbing fibres and parallel fibres causes LTD that decreases the excitatroy activity of purkinje cells
How does cerebellar LTD work?
The activation of the climbing fibre which gives the strong depolarisation, will depolarise the purkinje cell, opening voltage gated calcium channels, giving increase in calcium levels
The opening of metabotropic glutamate receptors leads to the activation of the enzyme phospholipase C, one of the things that phospholipase C does is produce this compound IP3 which is sugar basically but that acts on intracellular calcium stores and leads to the release of calcium
So we’ve got two different pathways coming together to give a big increase in calcium concentrations so one from the intracellular stores, one from the voltage gated calcium channels and so then we get changes to AMPA receptors which lead to their internalisation as a consequence of that, so the ultimate thing at the end is the same, we have internalisation of AMPA receptors but its happened via activation of different receptors and things like that
What is the disease relevance of synaptic plasticity?
Memory loss in AD- changes in LTP have been observed before we have synaptic loss or anything
Kindling in Epilepsy
Drug addiction- LTD of dopaminergic synpases between neurons from the ventral tegmentum area and the nucleus accumbens, depression of these synapses means drug addicts need higher and higher doses to overcome that depression of synapses
