Sure, except that sounds like NMDA excitability CAUSES memory formation. With that as a given, would you still argue that too much excitability (ie, excitotoxicity), would have a paradoxical effect on memory formation?
yeah....
Increased extracellular glutamate levels leads to the activation of Ca2+ permeable NMDA receptors on myelin sheaths and
oligodendrocytes, leaving oligodendrocytes susceptible to Ca2+ influxes and subsequent excitotoxicity.
[14][15] One of the damaging results of excess calcium in the cytosol is initiating apoptosis through cleaved
caspase processing.
[16] Another damaging result of excess calcium in the cytosol is the opening of the
mitochondrial permeability transition pore, a pore in the membranes of
mitochondria that opens when the organelles absorb too much calcium. Opening of the pore may cause mitochondria to swell and release
reactive oxygen species and other proteins that can lead to
apoptosis. The pore can also cause mitochondria to release more calcium. In addition, production of
adenosine triphosphate (ATP) may be stopped, and
ATP synthase may in fact begin
hydrolysing ATP instead of producing it.
[17]
Inadequate
ATP production resulting from brain trauma can eliminate
electrochemical gradients of certain ions.
Glutamate transporters require the maintenance of these ion gradients to remove glutamate from the extracellular space. The loss of ion gradients results in not only the halting of glutamate uptake, but also the reversal of the transporters. The Na+-glutamate transporters on neurons and astrocytes can reverse their glutamate transport and start secreting glutamate at a concentration capable of inducing excitotoxicity.
[18] This results in a buildup of glutamate and further damaging activation of glutamate receptors.
Second paragraph seems to indicate what I said earlier- its the ion gradient thats lost. First para seems to indicate general ways to damage cells.
Look- I dont know that everyone is expected to retain all these details but looking at the general properties of cell damage it seems that based on that knowledge alone one could come up with the right answer by guessing right. I didnt know about glutamate toxicity but know that ions are easily damaged and NMDA is ion dependent- decreased ATp leads to ion gradient loss. so that makes sense.
In terms of excitotoxicity- i think most of these cell types would allow for greater Ca entry (not just glutamate specific) over time and cause increased Ca damage.
The only reason this may be mitigated and not seen in catecholamines and acytlcholine is because they rapidly down regulate receptors- the same with hormones.
So in the absence of that data - say for unique receptors like NMDA it makes sense that they would be more susceptible to damage. Which menas you can take this concept to almost any tissue/drug and generalize broadly (except when you have downregulation of receptors which we know for sure happens in catecholamesn and acetylcholine)
I know what I said is not an absolute- but its these general concepts that are invaluable in coming up wtih answers- IMO
