Abstract
An action potential (AP) triggers neurotransmitter release from synaptic vesicles (SVs) docking to a specialized release site of presynaptic plasma membrane, the active zone (AZ). The AP simultaneously controls the release site replenishment with SV for sustainable synaptic transmission in response to incoming neuronal signals. Although many studies have suggested that the replenishment time is relatively slow, recent studies exploring high speed resolution have revealed SV dynamics with milliseconds timescale after an AP. Accurate regulation is conferred by proteins sensing Ca2+ entering through voltage-gated Ca2+ channels opened by an AP. This review summarizes how millisecond Ca2+ dynamics activate multiple protein cascades for control of the release site replenishment with release-ready SVs that underlie presynaptic short-term plasticity.
Highlights
Ultrastructural studies have demonstrated that some SVs are in contact with the presynaptic plasma membrane in the active zone (AZ) [1,2], and docked vesicles are thought to represent fusion-competent vesicles [3,4,5]
The phosphomimetic-CASTS45D expression reduced the peak amplitude and the integral of excitatory postsynaptic potential (EPSP), and SV number in the readily releasable vesicle pools (RRP) [56]. These results suggest that CAST controls the number of docked SVs regulating AZ size, but not the SV release probability, and that the CASTS45 phosphorylation decreases the number of release-ready SVs
After a long burst of action potential (AP), myosin IIB acts in the fast loading of release-ready SVs close to the release site where is restored by dynamin 1-mediated membrane recycling pathway, while VI supports the slow SV loading through dynamin 3-mediated pathway
Summary
Ultrastructural studies have demonstrated that some SVs are in contact with the presynaptic plasma membrane in the AZ [1,2], and docked vesicles are thought to represent fusion-competent vesicles [3,4,5]. The ‘zap-and-freeze’ method, after generating a single AP high-pressure freezing at defined time points, was developed by Watanabe and co-workers [10] Applying this approach to mouse hippocampal neurons in culture, they characterized the spatial and temporal organization of SV fusion sites following a single AP and demonstrated that multiple vesicles fuse within the same AZ, and ~40% of docked vesicles are lost immediately after stimulation due to fusion and, potentially, undocking. This review introduces, at first, recent findings on temporal regulation of SV states within 100 ms of a single AP, and our findings on millisecond Ca2+ dynamicsdependent transmitter release site replenishment with release-ready SVs that involves multiple protein cascades, such as phosphorylation of AZ proteins, activation of myosin motors and that of key proteins linking exocytosis and endocytosis These protein reactions controlled by Ca2+ sensors underlie the presynaptic short-term plasticity. Regulation of Ca2+ elevation significantly controls the state and replenishment of SVs and contributes to presynaptic plasticity
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