Synaptic Vesicle Generation from Central Nerve Terminal Endosomes

Central nerve terminals contain a small number of synaptic vesicles (SVs) that must sustain the fidelity of neurotransmission across a wide range of stimulation intensities. For this to be achieved, nerve terminals integrate a number of complementary endocytosis modes whose activation spans the breadth of these neuronal stimulation patterns. Two such modes are ultrafast endocytosis and activity‐dependent bulk endocytosis, which are triggered by stimuli at either end of the physiological range. Both endocytosis modes generate endosomes directly from the nerve terminal plasma membrane, before the subsequent production of SVs from these structures. This review will discuss the current knowledge relating to the molecular mechanisms involved in the generation of SVs from nerve terminal endosomes, how this relates to other mechanisms of SV production and the functional role of such SVs. Studies investigating the direct generation of endosomes during endocytosis in central nerve terminals have enjoyed a renaissance in the past 5 years. However, relatively little is known regarding the molecular basis of subsequent synaptic vesicle (SV) generation from these endosomes. This article discusses potential mechanisms and how endosome‐derived SVs contribute to central nerve terminal function.