Abstract
For releasing neurotransmitter synaptic vesicles have to fuse with the plasma membrane (exocytosis). This happens on the tens of microseconds time scale. Once vesicles have released their contents new vesicles have to dock at the plasma membrane and macromolecular complexes have to be built up (a process called ‘priming’), which enables vesicles to fuse. Electrophysiologists try to assign roles of proteins to either priming or exocytosis by manipulating proteins and analyzing observed changes in release either in terms of changes in the number of available vesicles (indicating a role in priming) or else as changes in release probability (indicating a role in exocytosis). However, considering priming as a reversible, multistep process, it turns out that current methods to determine these two parameters may blur the distinction between priming and exocytosis. Nevertheless, a detailed kinetic analysis (Lin et al. 2022. PNAS. 119. e2207987119) allows one to differentiate between various stages of priming and release and offers explanations for some interesting properties of synaptic short-term plasticity.