Prior to exocytosis, the synaptic vesicles are filled with neurotransmitter and translocate to the active zone, where they dock at morphologically defined sites on the target plasma membrane. The v-SNARE synaptobrevin/VAMP faces the target plasma membrane, which contains the v-SNAREs SNAP25 and syntaxin, which associates with MUNC18/n-Sec1. During the priming stage of vesicle fusion, the SNARE proteins partially zipper together and complexin clamps the SNARE complex in an activation-poised state to prevent membrane fusion. Action potential–induced calcium influx triggers calcium, phospholipid, and SNARE complex binding by synaptotagmin, which causes displacement of complexin and opening of the fusion pore. Vesicle/target membrane fusion allows neurotransmitter to enter the synaptic cleft and interact with the postsynaptic density of the partner neuron (inset).