Post-tetanic potentiation lowers the energy barrier for synaptic vesicle fusion independently of Synaptotagmin-1
- Amsterdam University Medical Center- Location VUmc, Netherlands
- VU University Medical Center, Netherlands
Abstract
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.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.
Article and author information
Author details
Lennart Niels Cornelisse
Funding
H2020 European Research Council (ERC Advanced Grant,322966)
- Matthijs Verhage
Nederlandse Organisatie voor Wetenschappelijk Onderzoek (CLS2007,635100020)
- Lennart Niels Cornelisse
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Yukiko Goda, RIKEN, Japan
Ethics
Animal experimentation: Animals were housed and bred according to institutional and Dutch governmental guidelines, and all procedures are approved by the ethical committee of the Vrije Universiteit, Amsterdam, The Netherlands (Dierexperimentencomissie (DEC) license number: FGA11-03).
Version history
- Received: February 12, 2020
- Accepted: August 23, 2020
- Accepted Manuscript published: August 24, 2020 (version 1)
- Version of Record published: September 18, 2020 (version 2)
Copyright
© 2020, Huson et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Post-tetanic potentiation lowers the energy barrier for synaptic vesicle fusion independently of Synaptotagmin-1
eLife 9:e55713.
https://doi.org/10.7554/eLife.55713
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