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Cell Rep. 2017 Jan 17;18(3):723-736. doi: 10.1016/j.celrep.2016.12.067.

Synaptotagmin 2 Is the Fast Ca2+ Sensor at a Central Inhibitory Synapse.

Author information

1
IST Austria (Institute of Science and Technology Austria), Am Campus 1, 3400 Klosterneuburg, Austria.
2
Max Planck Florida Institute for Neuroscience, Research Group Molecular Mechanisms of Synaptic Function, Jupiter, FL 33458, USA.
3
IST Austria (Institute of Science and Technology Austria), Am Campus 1, 3400 Klosterneuburg, Austria. Electronic address: peter.jonas@ist.ac.at.

Abstract

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 Ca2+ 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 ∼10%, identifying Syt2 as the major Ca2+ 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.

KEYWORDS:

Ca(2+) sensor; GABAergic synapses; basket cells; cerebellum; endocytosis; exocytosis; feedforward inhibition; pool replenishment; synaptotagmin; transmitter release

PMID:
28099850
PMCID:
PMC5276807
DOI:
10.1016/j.celrep.2016.12.067
[Indexed for MEDLINE]
Free PMC Article

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