Aversive stimuli drive hypothalamus-to-habenula excitation to promote escape behavior
Salvatore Lecca,
Frank Julius Meye,
Massimo Trusel,
Anna Tchenio,
Julia Harris,
Martin Karl Schwarz,
Denis Burdakov,
Francois Georges,
Manuel Mameli
Affiliations
Salvatore Lecca
Institut du Fer à Moulin, Inserm UMR-S 839, Paris, France; Department of Fundamental Neuroscience, The University of Lausanne, Lausanne, Switzerland
Frank Julius Meye
Institut du Fer à Moulin, Inserm UMR-S 839, Paris, France; Department Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Netherlands
Massimo Trusel
Institut du Fer à Moulin, Inserm UMR-S 839, Paris, France; Department of Fundamental Neuroscience, The University of Lausanne, Lausanne, Switzerland
Anna Tchenio
Institut du Fer à Moulin, Inserm UMR-S 839, Paris, France; Department of Fundamental Neuroscience, The University of Lausanne, Lausanne, Switzerland
Julia Harris
The Francis Crick Institute, London, United Kingdom
Martin Karl Schwarz
Clinic for Epilepsy Life and Brain Center, University Clinic of Bonn, Bonn, Germany
Denis Burdakov
The Francis Crick Institute, London, United Kingdom
Francois Georges
Université de Bordeaux, Neurodegeneratives Diseases Institute, Bordeaux, France; Centre National de la Recherche Scientifique, Neurodegeneratives Diseases Institute, Bordeaux, France
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.
