A comparison between direct and indirect measurements of neurotransmitter vesicle release dynamics: a computational study.

Presynaptic vesicular release of neurotransmitters is a stochastic process involving complex mechanisms triggered by an elevation of calcium concentration. The mechanisms behind neurotransmitters release play a critical role in synaptic function and plasticity. Understanding its properties, both in term of its dynamics and its underlying mechanisms, may therefore help further our understanding of synaptic plasticity. However, measuring vesicle release dynamics is experimentally challenging. One experimental protocol used to determine the dynamic properties of vesicle release is to measure postsynaptic current. However, this method inherently not only captures properties of the release itself, but also the contributions from the postsynaptic receptors. Here we propose to use a synapse simulation platform known as EONS/RHENOMS to capture the functional properties of vesicle release, separate from the dynamics known to be associated with postsynaptic receptors, and compare the results with those determined experimentally. We find that despite attempts to reduce interference of postsynaptic dynamics, the receptor channel properties, particularly desensitization, may influence the overall measured results significantly. Re-estimating release rate by taking into account the contributions of postsynaptic receptors may give further insight into release dynamics and further our overall understanding on synaptic plasticity.