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Having learned something about retrograde signaling I wonder why it is so hard to observe and to decide whether presynaptic potentiation actually takes place in the course of long term potentiation (by whatever mechanisms). By presynaptic potentiation I mean that after LTP the presynaptic neuron releases more neurotransmitter molecules than before, either more molecules per vesicle and/or by having more vesicles.

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Only if there is evidence for presynaptic potentiation there would be a need to look for mechanisms of retrograde signaling (which still seem to be unknown, as well if they exist at all as what their specifics would be).

But before looking for evidence of presynaptic potentiation one question may be asked: How big is the surplus of neurotransmitters in a normal "juvenile non-potentiated" synapse? Being aware that an answer will depend heavily on what is meant with the words "normal", "juvenile", and "non-potentiated", I hope that it nevertheless may make sense to ask:

What's a typical ratio of the number of neurotransmitter molecules released by a presynaptic neuron during one synaptic event, and the number of molecules received by the postsynaptic neuron (the rest just being re-absorbed, metabolized or diffusing away)?

Instead of "(juvenile) non-potentiated" synapses one might consider "(adult) balanced synapses" with a "normal" surplus. Or even more generally "synapses before an LTP event starts"

If the ratio is big enough there might be no need for presynaptic potentiation in the course of LTP. On the other side: If presynaptic potentiation would not take place, long term potentiation would have an early limit (at a single synapse).

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