Neuronal Regulation of Fast Synaptotagmin Isoforms Controls the Relative Contributions of Synchronous and Asynchronous Release.

Summary Neurotransmitter release can be synchronous and occur within milliseconds of action potential invasion, or asynchronous and persist for tens of milliseconds. The molecular determinants of release kinetics remain poorly understood. It has been hypothesized that asynchronous release dominates when fast Synaptotagmin isoforms are far from calcium channels or when specialized sensors, such as Synaptotagmin 7, are abundant. Here we test these hypotheses for GABAergic projections onto neurons of the inferior olive, where release in different subnuclei ranges from synchronous to asynchronous. Surprisingly, neither of the leading hypotheses accounts for release kinetics. Instead, we find that rapid Synaptotagmin isoforms are abundant in subnuclei with synchronous release but absent where release is asynchronous. Viral expression of Synaptotagmin 1 transforms asynchronous synapses into synchronous ones. Thus, the nervous system controls levels of fast Synaptotagmin isoforms to regulate release kinetics and thereby controls the ability of synapses to encode spike rates or precise timing. Highlights • The release kinetics of GABA in the inferior olive (IO) are regionally segregated • In the absence of Syt7, asynchronous release is prominent but with altered kinetics • Viral expression of fast Syts transforms asynchronous synapses into synchronous ones • Asynchronous GABA release in the IO is a consequence of a lack of fast Syt isoforms The synchrony of GABA release in the inferior olive is regionally specialized. We find that Syt7 controls the kinetics of asynchronous release and that release synchrony is controlled by the presence or absence of fast Syt isoforms. [ABSTRACT FROM AUTHOR]