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Aversive stimuli drive hypothalamus-to-habenula excitation to promote escape behavior

  1. Salvatore Lecca
  2. Frank Julius Meye
  3. Massimo Trusel
  4. Anna Tchenio
  5. Julia Harris
  6. Martin Karl Schwarz
  7. Denis Burdakov
  8. Francois Georges
  9. Manuel Mameli  Is a corresponding author
  1. Institut du Fer à Moulin, Inserm UMR-S 839, France
  2. The University of Lausanne, Switzerland
  3. The Francis Crick Institute, Kings Cross, United Kingdom
  4. University Clinic of Bonn, Germany
  5. Université de Bordeaux, Neurodegeneratives Diseases Institute, France
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Cite this article as: eLife 2017;6:e30697 doi: 10.7554/eLife.30697

Abstract

A sudden aversive event produces escape behaviors, an innate response essential for survival in virtually all-animal species. Nuclei including the lateral habenula (LHb), the lateral hypothalamus (LH), and the midbrain are not only reciprocally connected, but also respond to negative events contributing to goal-directed behaviors. However, whether aversion encoding requires these neural circuits to ultimately prompt escape behaviors remains unclear. We observe that aversive stimuli, including foot-shocks, excite LHb neurons and promote escape behaviors in mice. The foot-shock-driven excitation within the LHb requires glutamatergic signaling from the LH, but not from the midbrain. This hypothalamic excitatory projection predominates over LHb neurons monosynaptically innervating aversion-encoding midbrain GABA cells. Finally, the selective chemogenetic silencing of the LH-to-LHb pathway impairs aversion-driven escape behaviors. These findings unveil a habenular neurocircuitry devoted to encode external threats and the consequent escape; a process that, if disrupted, may compromise the animal’s survival.

Article and author information

Author details

  1. Salvatore Lecca

    Institut du Fer à Moulin, Inserm UMR-S 839, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  2. Frank Julius Meye

    Department of Fundamental Neuroscience, The University of Lausanne, Lausanne, Switzerland
    Competing interests
    The authors declare that no competing interests exist.
  3. Massimo Trusel

    Institut du Fer à Moulin, Inserm UMR-S 839, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Anna Tchenio

    Institut du Fer à Moulin, Inserm UMR-S 839, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Julia Harris

    The Francis Crick Institute, Kings Cross, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Martin Karl Schwarz

    Clinic for epilepsy life and Brain center, University Clinic of Bonn, Bonn, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Denis Burdakov

    The Francis Crick Institute, Kings Cross, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  8. Francois Georges

    Université de Bordeaux, Neurodegeneratives Diseases Institute, Bordeaux, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Manuel Mameli

    Institut du Fer à Moulin, Inserm UMR-S 839, Paris, France
    For correspondence
    manuel.mameli@unil.ch
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0570-6964

Funding

This work was supported by INSERM Atip-Avenir, the City of Paris, the European Research Council (Starting grant SalienSy 335333) to M.M., the HFSP (Young Investigator Award RGY0076) to D.B.

Ethics

Animal experimentation: Mice were used in accordance with the guidelines of the Ministry of Agriculture and Forestry for animal handling and the ethic committee Charles Darwin #5 of the University Pierre et Marie Curie. Part of the current study was carried at the Department of Fundamental Neuroscience of the University of Lausanne (Lausanne, Switzerland) according to the regulations of the Cantonal Veterinary Offices of Vaud and Zurich (Switzerland; License VD3171).

Reviewing Editor

  1. Olivier Manzoni, Inmed, INSERM, Marseilles, France

Publication history

  1. Received: July 24, 2017
  2. Accepted: August 30, 2017
  3. Accepted Manuscript published: September 5, 2017 (version 1)
  4. Version of Record published: September 20, 2017 (version 2)

Copyright

© 2017, Lecca 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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