1. Neuroscience
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Post-tetanic potentiation lowers the energy barrier for synaptic vesicle fusion independently of Synaptotagmin-1

  1. Vincent Huson
  2. Marieke Meijer
  3. Rien Dekker
  4. Mirelle ter Veer
  5. Marvin Ruiter
  6. Jan R T van Weering
  7. Matthijs Verhage
  8. Lennart Niels Cornelisse  Is a corresponding author
  1. Amsterdam University Medical Center- Location VUmc, Netherlands
  2. VU University Medical Center, Netherlands
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Cite this article as: eLife 2020;9:e55713 doi: 10.7554/eLife.55713
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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

  1. Vincent Huson

    Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Amsterdam University Medical Center- Location VUmc, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3556-1436
  2. Marieke Meijer

    Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Amsterdam University Medical Center- Location VUmc, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  3. Rien Dekker

    Department of Functional Genomics, Clinical Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam University Medical Center- Location VUmc, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6284-3279
  4. Mirelle ter Veer

    Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University Medical Center, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  5. Marvin Ruiter

    Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, VU University Medical Center, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  6. Jan R T van Weering

    Department of Clinical Genetics, Amsterdam University Medical Center- Location VUmc, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  7. Matthijs Verhage

    Department of Clinical Genetics, Amsterdam University Medical Center- Location VUmc, Amsterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  8. Lennart Niels Cornelisse

    Department of Functional Genomics, Clinical Genetics, Center for Neurogenomics and Cognitive Research, Amsterdam University Medical Center- Location VUmc, Amsterdam, Netherlands
    For correspondence
    l.n.cornelisse@vu.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9425-2935

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.

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).

Reviewing Editor

  1. Yukiko Goda, RIKEN, Japan

Publication history

  1. Received: February 12, 2020
  2. Accepted: August 23, 2020
  3. Accepted Manuscript published: August 24, 2020 (version 1)
  4. 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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