Final Report Summary - SINGLESITE (Pre- and postsynaptic signaling at single synaptic contacts) This project established a series of new methods for the electrophysiological recording of vesicular release in small synapses comprising a single presynaptic active zone and a single postsynaptic density ('simple synapses'). We found that the output of simple synapses is limited, suggesting the presence of several docking/release sites per simple synapse. Docking/release site numbers vary among simple synapses. Docking/release site numbers are very similar to the numbers of clusters of voltage-gated calcium channels in the active zone, suggesting a close association of one docked synaptic vesicle with one cluster of calcium channels. The statistics of vesicular release at simple synapses are best explained by a sequential model called 2-step model. In this model, each vesicle associates first to a 'replacement site' and then to an associated docking site before being released. Docking site occupancy emerges as a key parameter governing synaptic function. Changes in docking site occupancy are in particular responsible for short term synaptic plasticity (synaptic facilitation and synaptic depression).
