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

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).

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.

Metrics

  • 1,379
    views
  • 191
    downloads
  • 9
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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
(2020)
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

Share this article

https://doi.org/10.7554/eLife.55713

Further reading

    1. Neuroscience
    Gyeong Hee Pyeon, Hyewon Cho ... Yong Sang Jo
    Research Article Updated

    Recent studies suggest that calcitonin gene-related peptide (CGRP) neurons in the parabrachial nucleus (PBN) represent aversive information and signal a general alarm to the forebrain. If CGRP neurons serve as a true general alarm, their activation would modulate both passive nad active defensive behaviors depending on the magnitude and context of the threat. However, most prior research has focused on the role of CGRP neurons in passive freezing responses, with limited exploration of their involvement in active defensive behaviors. To address this, we examined the role of CGRP neurons in active defensive behavior using a predator-like robot programmed to chase mice. Our electrophysiological results revealed that CGRP neurons encode the intensity of aversive stimuli through variations in firing durations and amplitudes. Optogenetic activation of CGRP neurons during robot chasing elevated flight responses in both conditioning and retention tests, presumably by amplifying the perception of the threat as more imminent and dangerous. In contrast, animals with inactivated CGRP neurons exhibited reduced flight responses, even when the robot was programmed to appear highly threatening during conditioning. These findings expand the understanding of CGRP neurons in the PBN as a critical alarm system, capable of dynamically regulating active defensive behaviors by amplifying threat perception, and ensuring adaptive responses to varying levels of danger.

    1. Neuroscience
    Li Shen, Shuo Li ... Yi Jiang
    Research Article

    When observing others’ behaviors, we continuously integrate their movements with the corresponding sounds to enhance perception and develop adaptive responses. However, how the human brain integrates these complex audiovisual cues based on their natural temporal correspondence remains unclear. Using electroencephalogram (EEG), we demonstrated that rhythmic cortical activity tracked the hierarchical rhythmic structures in audiovisually congruent human walking movements and footstep sounds. Remarkably, the cortical tracking effects exhibit distinct multisensory integration modes at two temporal scales: an additive mode in a lower-order, narrower temporal integration window (step cycle) and a super-additive enhancement in a higher-order, broader temporal window (gait cycle). Furthermore, while neural responses at the lower-order timescale reflect a domain-general audiovisual integration process, cortical tracking at the higher-order timescale is exclusively engaged in the integration of biological motion cues. In addition, only this higher-order, domain-specific cortical tracking effect correlates with individuals’ autistic traits, highlighting its potential as a neural marker for autism spectrum disorder. These findings unveil the multifaceted mechanism whereby rhythmic cortical activity supports the multisensory integration of human motion, shedding light on how neural coding of hierarchical temporal structures orchestrates the processing of complex, natural stimuli across multiple timescales.