Synaptic Vesicle Endocytosis and Endosomal Recycling in Central Nerve Terminals: Discrete Trafficking Routes?

Synaptic vesicle (SV) retrieval from the presynaptic plasma membrane occurs via a variety of different and complementary modes. The dominant retrieval mode during high-intensity stimulation is activity-dependent bulk endocytosis (ADBE). ADBE involves the generation of endosomes direct from the plasma membrane which then donate membrane and cargo to form SVs that replenish the reserve SV pool. Recent evidence has suggested that ADBE may involve an additional endosomal processing step to produce a mature, functional SV. This suggests that ADBE may utilize key molecules or indeed whole pathways from classical endocytic recycling routes that are ubiquitous across all cell types. This review will assess the current evidence for a contribution of endocytic recycling to the SV life cycle, with a particular focus on ADBE. In doing so it highlights points where both routes may either converge or exploit existing mechanisms to ensure efficient generation of SVs during high-intensity stimulation.