Abstract
SUMMARYSynaptotagmin 7 (Syt7) is thought to be a Ca2+ sensor that mediates asynchronous transmitter release and facilitation at synapses. However, Syt7 is strongly expressed in fast-spiking, parvalbumin-expressing GABAergic interneurons, and the output synapses of these neurons produce only minimal asynchronous release and show depression rather than facilitation. To resolve this apparent contradiction, we examined the effects of genetic elimination of Syt7 on synaptic transmission at the GABAergic basket cell (BC)-Purkinje cell (PC) synapse in cerebellum. Our results indicate that at the BC-PC synapse, Syt7 contributes to asynchronous release, pool replenishment, and facilitation. In combination, these three effects ensure efficient transmitter release during high-frequency activity and guarantee frequency independence of inhibition. Our results identify a distinct function of Syt7: ensuring the efficiency of high-frequency inhibitory synaptic transmission.
Highlights
Synaptotagmins play a key role in Ca2+-dependent transmitter release (Südhof, 2002; Chapman, 2002; Koh and Bellen, 2003)
To examine the possible function of Synaptotagmin 7 (Syt7) in inhibitory synaptic transmission, we investigated the effects of deletion of the Syt7 gene at identified GABAergic basket cell (BC)-Purkinje cell (PC) synapses in cerebellar slices (Arai and Jonas, 2014)
We examined the functional contribution of Syt7 to transmitter release at the GABAergic BC-PC synapse in the cerebellum, a synapse ideal for the biophysical analysis of GABAergic synaptic transmission (Eggermann and Jonas, 2011; Arai and Jonas, 2014; Chen et al, 2017)
Summary
Synaptotagmins play a key role in Ca2+-dependent transmitter release (Südhof, 2002; Chapman, 2002; Koh and Bellen, 2003). Syt, Syt, and Syt, have been demonstrated to operate as fast release sensors (Geppert et al, 1994; Xu et al, 2007; Kerr et al, 2008; Kochubey et al, 2016; Chen et al, 2017). In cultured hippocampal synapses, Syt was suggested to promote replenishment of the releasable vesicle pool (Liu et al, 2014). In hippocampal and corticothalamic synapses in slices, Syt was recently proposed to operate as a Ca2+ sensor of synaptic facilitation (Jackman et al, 2016). How these divergent functions can be reconciled remains to be determined. One possibility is that Syt has different functions at different synapses
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