TY - JOUR
T1 - Aversive stimuli drive hypothalamus-to-habenula excitation to promote escape behavior
AU - Lecca, Salvatore
AU - Meye, Frank Julius
AU - Trusel, Massimo
AU - Tchenio, Anna
AU - Harris, Julia
AU - Schwarz, Martin Karl
AU - Burdakov, Denis
AU - Georges, Francois
AU - Mameli, Manuel
N1 - Funding Information:
This work was supported by INSERM Atip-Avenir, the City of Paris, the European Research Council (Starting grant SalienSy 335333) to MM, the HFSP (Young Investigator Award RGY0076) to DB. We thank A Adamantidis, J Letzkus, C Lüscher and the entire Mameli Laboratory for feedback on the manuscript and constructive discussions.
Publisher Copyright:
© Lecca et al.
PY - 2017/9/5
Y1 - 2017/9/5
N2 - 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.
AB - 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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U2 - 10.7554/eLife.30697
DO - 10.7554/eLife.30697
M3 - Article
C2 - 28871962
AN - SCOPUS:85032493095
SN - 2050-084X
VL - 6
JO - eLife
JF - eLife
M1 - e30697
ER -