Synaptic Vesicle Recycling at the Developing Presynapse

Neurotransmitter release plays a fundamental role in brain communication. This is mediated via the exocytosis of neurotransmitter-containing synaptic vesicles (SVs) at the presynapse. After fusion with the presynaptic plasma membrane, SVs are regenerated by endocytosis and recycled back into functional pools. The great majority of research that has studied this essential process has focused on SV recycling at the mature presynaptic terminal. In contrast, SV recycling in immature neurons remains poorly understood, even though its disruption is heavily associated with a series of neurodevelopmental disorders. Evidence is accumulating that developing neurons display distinct presynaptic mechanisms for SV recycling. For example, developing presynapses display loose coupling between evoked calcium influx and SV fusion, with spontaneous SV exocytosis and clathrin-mediated endocytosis being the dominant exocytosis and endocytosis mechanisms respectively. In contrast, SV fusion in mature nerve terminals is tightly coupled to evoked calcium influx, with evoked SV exocytosis and endosomal modes of endocytosis dominant. This article reviews research at each stage of the SV recycling process at both mature and immature nerve terminals, beginning with the coupling of activity-dependent calcium influx to neurotransmitter release. In doing so, it aims to provide an integrated perspective of current knowledge regarding SV recycling through development across different neuronal systems, while posing key future questions to address for the presynaptic development field.