Prioritized docking of synaptic vesicles provided by a rapid recycling pathway

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 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 size of 180 vesicles per active zone. This effect was counteracted by the activation of a rapid recycling pathway, which utilized vesicles ∼10 s after endocytosis and was able to generate 200 vesicles per active zone. Blocking the rapid recycling of vesicles revealed an enhanced probability of docking of recently endocytosed vesicles compared to those coming from the recycling pool. Thus, our results demonstrate a differential sorting of vesicles inside the readily releasable pool depending on their origin.