Prioritized docking of synaptic vesicles provided by a rapid recycling pathway

Abstract

It is known that endocytosis of synaptic vesicles, and docking of these vesicles to their release sites, are regulated in a similar manner, but it has remained unclear whether the two processes are linked together mechanistically. To address this issue, we studied vesicular release during repeated trains of presynaptic action potentials. Synaptic responses decreased when the inter-train interval was shortened, indicating a gradual exhaustion of the recycling pool of vesicles, with a resting capacity of about 180 vesicles per active zone. This effect was partially counteracted by activation of a rapid recycling pathway that depended on the activation of myosin light chain kinase and that had a capacity of 200 vesicles per active zone. Vesicles arising from the rapid recycling route were preferentially docked in comparison with vesicles coming from an upstream pool, demonstrating a differential sorting of vesicles inside the readily releasable pool depending on their origin.