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

Publication date: 17 January 2017
Source:Cell Reports, Volume 18, Issue 3
Author(s): Chong Chen, Itaru Arai, Rachel Satterfield, Samuel M. Young, Peter Jonas
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.

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Teaser

Chen et al. identify synaptotagmin 2 as the major Ca²⁺ sensor of transmitter release at cerebellar inhibitory synapses. Furthermore, they demonstrate that synaptotagmin 2 triggers faster release and ensures faster refilling of the vesicular pool than synaptotagmin 1.


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