Abstract

Neurotransmission in complex animals depends on a choir of functionally distinct synapses releasing neurotransmitters in a highly coordinated manner. During synaptic signaling, vesicles fuse with the plasma membrane to release their contents. The rate of vesicle fusion is high and can exceed the rate at which synaptic vesicles can be re-supplied by distant sources. Thus, local compensatory endocytosis is needed to replenish the synaptic vesicle pools. Over the last four decades, various experimental methods and model systems have been used to study the cellular and molecular mechanisms underlying synaptic vesicle cycle. Clathrin-mediated endocytosis is thought to be the predominant mechanism for synaptic vesicle recycling. However, recent studies suggest significant contribution from other modes of endocytosis, including fast compensatory endocytosis, activity-dependent bulk endocytosis, ultrafast endocytosis, as well as kiss-and-run. Currently, it is not clear whether a universal model of vesicle recycling exist for all types of synapses. It is possible that each synapse type employs a particular mode of endocytosis. Alternatively, multiple modes of endocytosis operate at the same synapse, and the synapse toggles between different modes depending on its activity level. Here we compile review and research articles based on well-characterized model systems: frog neuromuscular junctions, C. elegans neuromuscular junctions, Drosophila neuromuscular junctions, lamprey reticulospinal giant axons, goldfish retinal ribbon synapses, the calyx of Held, and rodent hippocampal synapses. We will compare these systems in terms of their known modes and kinetics of synaptic vesicle endocytosis, as well as the underlying molecular machineries. We will also provide the future development of this field.

Highlights

  • Synaptic vesicle recycling has been studied extensively for over 40 years in various model systems

  • Numbers of vesicles released by protocols that induce activity-dependent bulk endocytosis are estimated based on the percentage of HRP-labeled vesicles, the steady-state release rate, the total increase in membrane capacitance, or the average Pr at a given type of synapse

  • For example, is almost invariably required for the major endocytic pathways at all seven types of synapses, the only exceptions are dynamin-independent forms of endocytosis found at the calyx of Held and cultured cortical neurons during highly intense stimulation (Xu et al, 2008; Wu et al, 2014)

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Summary

Introduction

Synaptic vesicle recycling has been studied extensively for over 40 years in various model systems. Numbers of vesicles released by protocols that induce activity-dependent bulk endocytosis are estimated based on the percentage of HRP-labeled vesicles (as in frog muscular junctions), the steady-state release rate (as in Drosophila neuromuscular junctions and goldfish retinal bipolar neuron terminals), the total increase in membrane capacitance (as in the calyx of Held), or the average Pr at a given type of synapse (as in lamprey giant synapses and rodent hippocampal synapses). The molecular requirements of synaptic vesicle recycling in different model systems are, as expected, similar.

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