Post-tetanic potentiation lowers the energy barrier for synaptic vesicle fusion independently of synaptotagmin-1

Vincent Huson, Marieke Meijer, Rien Dekker, Mirelle Ter Veer, Marvin Ruiter, Jan van Weering, Matthijs Verhage, L. Niels Cornelisse

Research output: Contribution to JournalArticleAcademicpeer-review


Previously, we showed that modulation of the energy barrier for synaptic vesicle fusion boosts release rates supralinearly (Schotten, 2015). Here we show that mouse hippocampal synapses employ this principle to trigger Ca2+-dependent vesicle release and post-tetanic potentiation (PTP). We assess energy barrier changes by fitting release kinetics in response to hypertonic sucrose. Mimicking activation of the C2A domain of the Ca2+-sensor Synaptotagmin-1 (Syt1), by adding a positive charge (Syt1D232N) or increasing its hydrophobicity (Syt14W), lowers the energy barrier. Removing Syt1 or impairing its release inhibitory function (Syt19Pro) increases spontaneous release without affecting the fusion barrier. Both phorbol esters and tetanic stimulation potentiate synaptic strength, and lower the energy barrier equally well in the presence and absence of Syt1. We propose a model where tetanic stimulation activates Syt1-independent mechanisms that lower the energy barrier and act additively with Syt1-dependent mechanisms to produce PTP by exerting multiplicative effects on release rates.

Original languageEnglish
Article numbere55713
Pages (from-to)1-56
Number of pages56
Publication statusPublished - Aug 2020


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