Synaptotagmin 2 is the fast Ca^2+ sensor at a central inhibitory synapse Journal Article

Author(s): Chen, Chong; Arai, Itaru; Satterield, Rachel; Young, Samuel M; Jonas, Peter
Article Title: Synaptotagmin 2 is the fast Ca^2+ sensor at a central inhibitory synapse
Affiliation IST Austria
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 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 ∼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. #bioimagingfacility-author
Keywords: Exocytosis; Endocytosis; Cerebellum; basket cells; GABAergic synapses; transmitter release; synaptotagmin; Ca2+ sensor; pool replenishment; feedforward inhibition
Journal Title: Cell Reports
Volume: 18
Issue 3
ISSN: 2211-1247
Publisher: Cell Press  
Date Published: 2017-01-17
Start Page: 723
End Page: 736
Copyright Statement: CC BY 4.0
DOI: 10.1016/j.celrep.2016.12.067
Notes: We thank Drs. Nils Brose and Erwin Neher for reading the manuscript. We also thank Z. Pang and T. Südhof for providing Syt2 knockout mice, A. Schlögl for programming, F. Marr for technical assistance, E. Kramberger for manuscript editing, M. Schunn and J. Primus (preclinical facility) for mouse colony management, and E. Papusheva (bioimaging facility) for help with data analysis. This project has received funding from the Austrian Science Fund (FWF) (P 24909-B24) and the European Research Council (ERC) under the seventh framework programme with grant agreement number 268548 (both P.J.) and the Max Planck Society (S.M.Y.).
Open access: yes (OA journal)