3. Plasticity at glutamatergic synapses 2 Flashcards
what kind of experimental evidence suggests involvement of postsynaptic mechanisms in expression of LTP in the area CA1?
Increase in AMPA-R sensitivity after LTP, upon stimulating with electrodes. Proposed by change in AMPA-R properties and number ->
Properties evidence: LTP is associated with an increase in AMPA-R conductance thanks to phosphorylation of GluR1 by CaMKII
secondly, there is also evidence saying that there is NO presynaptic changes in LTP, thus there must be postsynaptic changes occuring.
How are AMPA-Rs regulated to increase/decrease the efficacy of synaptic transmission?
coincidence activity -> CaMKII activity -> phosphorylation of GluA1 on ser831 0> increase of time that AMPA-R retain a high conductance state -> increased efficacy of synaptic transmission.
AND
lateral movement of AMPA-R from a region that senses a lower concentration to one that has a higher concentration of glutamate: 3 pathways -> endocytosis, exocytosis and lateral diffusion. This is regulated via covalent modification & rules: depending on subunits present.
Explain the ‘slot’ hypothesis of LTP
what kind of experimental evidence suggests involvement of morphological changes in expression of LTP and in learning behaviours?
growth and retraction of spines have been reported following LTP-inducing protocols, but yet no reports of LTP-induced morphological changes at individually imaged spines.
-> superresolution imaging in hippocampal slices (CA1 neurons mouse): increase in spine head volume and decrease in neck length.
-> optical erasure of aquired motor neuron tasks in mice
Why is presynaptic function considered as an attractive target for plastic modulation?
at most central synapses, vesicle release probability is low -> much potential for LTP
small changes in Ca2+ influx during presynaptic AP are highly effective in modulating transmitter output -> Nonlinear dependence of vesicle fusion on presynaptic calcium concentration
Explain how different molecular mechanisms may contribute to LTP expression depending on the time from induction.
Different mechanisms of LTP induction will be turned on depending on the time after induction, which relates to the concept of E-LTP and L-LTP. First, mostly AMPA-R are modulated by increase in conductance, baseline and number of receptors. Later this will be strengthend by structural changes of the synapse: expansion and increase in synapses.
