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Publication : Synaptotagmin 2 Is the Fast Ca<sup>2+</sup> Sensor at a Central Inhibitory Synapse.

First Author  Chen C Year  2017
Journal  Cell Rep Volume  18
Issue  3 Pages  723-736
PubMed ID  28099850 Mgi Jnum  J:250703
Mgi Id  MGI:6103413 Doi  10.1016/j.celrep.2016.12.067
Citation  Chen C, et al. (2017) Synaptotagmin 2 Is the Fast Ca(2+) Sensor at a Central Inhibitory Synapse. Cell Rep 18(3):723-736
abstractText  GABAergic synapses in brain circuits generate inhibitory output signals with submillisecond latency and temporal precision. Whether the molecular identity of the release sensor contributes to these signaling properties remains unclear. Here, we examined the Ca(2+) sensor of exocytosis at GABAergic basket cell (BC) to Purkinje cell (PC) synapses in cerebellum. Immunolabeling suggested that BC terminals selectively expressed synaptotagmin 2 (Syt2), whereas synaptotagmin 1 (Syt1) was enriched in excitatory terminals. Genetic elimination of Syt2 reduced action potential-evoked release to approximately 10%, identifying Syt2 as the major Ca(2+) sensor at BC-PC synapses. Differential adenovirus-mediated rescue revealed that Syt2 triggered release with shorter latency and higher temporal precision and mediated faster vesicle pool replenishment than Syt1. Furthermore, deletion of Syt2 severely reduced and delayed disynaptic inhibition following parallel fiber stimulation. Thus, the selective use of Syt2 as release sensor at BC-PC synapses ensures fast and efficient feedforward inhibition in cerebellar microcircuits.
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