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The fusion of synaptic vesicles (SVs) with the plasma membrane of the active zone (AZ) upon arrival of an action potential (AP) at the presynaptic compartment is a tightly regulated probabilistic process crucial for information transfer (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4773589). In a typical forebrain synapse, only ~15% of APs arriving at the presynaptic terminal cause fusion of a synaptic vesicle.

My question is, what factors make this process probabilistic? What happens at the molecular/cellular level that an action potential can lead to the fusion of synaptic vesicles one time and not another time? Is it due to some differences between different synaptic vesicles, how the vesicles are positioned inside the synapse, variations in the synapse's environment, differences between action potentials, etc?

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