Neuron, 19 December 2018, Vol.100(6), pp.1283-1291
Based on evidence that the docked and primed synaptic vesicle state is very dynamic, we propose a three-step process for the buildup of the molecular machinery that mediates synaptic vesicle fusion: (1) loose tethering and docking of vesicles to release sites, forming the nucleus of SNARE-complex assembly, (2) tightening of the complex by association of additional proteins, and partial SNARE-complex zippering, and (3) Ca -triggered fusion. We argue that the distinction between “phasic synapses” and “tonic synapses” reflects differences in resting occupancy and stability of the loosely and tightly docked states, and we assign corresponding timescales: with high-frequency synaptic activity and concomitantly increased Ca -concentrations, step (1) can proceed within 10–50 ms, step (2) within 1–5 ms, and step (3) within 0.2–1 ms. Synaptic vesicle priming determines synaptic strength and short-term plasticity. Neher and Brose propose a model of loosely and tightly primed vesicle states, which can be interconverted rapidly, and whose occupancy defines the distinction between “phasic” and “tonic” synapses.
Synaptic Vesicles ; Exocytosis ; Snare-Complex ; Tethering ; Phasic Synapses ; Tonic Synapses ; Facilitation ; Biology ; Anatomy & Physiology
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