Aversive stimuli drive hypothalamus-to-habenula excitation to promote escape behavior
- Institut du Fer à Moulin, Inserm UMR-S 839, France
- The University of Lausanne, Switzerland
- The Francis Crick Institute, Kings Cross, United Kingdom
- University Clinic of Bonn, Germany
- Université de Bordeaux, Neurodegeneratives Diseases Institute, France
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.
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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).
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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