Presynaptic Membrane Turnover and Transmitter Release at the Calyx of Held

Abstract

Presynaptic neurotransmitter release parallels vigorous vesicle recycling, by which synapses ensure efficient vesicle replenishment, release site clearance, protein sorting, and structural integrity. Four membrane retrieval pathways have been proposed at nerve terminals, but controversy remains regarding the endocytic modes, underlying molecules, and physiological functions despite decades of tremendous effort. In particular, the recent findings on ultrafast endocytosis and dynamin-independent vesicle generation from rapidly retrieved bulk membrane challenge the previous recycling diagram and raise many interesting new questions. Moreover, increasing evidence suggests several important roles of endocytosis during fast synaptic transmission, in addition to its well-characterized function in vesicle resupply. Dynamin is a large GTPase, and it is required for clathrin-mediate endocytosis and maintaining readily releasable vesicle pool at synapses. Perturbations of this fission machinery offer a useful way to gain insights into cell physiology of membrane turnover at central synapses. Here, we summarize our recent work at the calyx of Held synapse, a fast glutamatergic terminal in the auditory brainstem. We found that multiple dynamin isoforms co-express at the calyx of Held and show isoform specific up regulation during development. Depending on the synaptic activity, dynamin-mediated endocytosis is required for several synaptic functions including vesicle genesis, transmitter release, short-term plasticity, quantal size stability, and calyx structure formation in vivo. We will discuss the role of dynamin in synaptic development, vesicle exo-endocytosis coupling, and the potential feedback from endocytosis at endocytic zones to exocytosis at active zones during fast transmitter release.