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

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journal contribution
posted on 15.10.2020, 16:36 by Salvatore Lecca, Frank J Meye, Massimo Trusel, Anna Tchenio, Julia Harris, Martin K Schwarz, Denis Burdakov, Francois Georges, Manuel Mameli
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.