Three small vesicular pools in sequence govern synaptic response dynamics during action potential trains

Abstract

Significance Short-term changes in the strength of synaptic connections underlie many brain functions. The strength of a synapse in response to subsequent stimulation is largely determined by the remaining number of synaptic vesicles available for release. We developed a methodological approach to measure the dynamics of various vesicle pools following synaptic activity. We find that the readily releasable pool, which comprises vesicles that are docked or tethered to release sites, is fed by a small-sized pool containing approximately one to four vesicles per release site at rest. This upstream pool is significantly depleted even after a short stimulation train. Therefore, regulation of the size of the upstream pool emerges as a key factor in determining synaptic strength during and after sustained stimulation.