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

• Published in: eLife Vol. 6
• Main Authors: Lecca, Salvatore, Meye, Frank Julius, Trusel, Massimo, Tchenio, Anna, Harris, Julia, Schwarz, Martin Karl, Burdakov, Denis, Georges, Francois, Mameli, Manuel
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 05.09.2017; eLife Sciences Publications Ltd; eLife Sciences Publication; eLife Sciences Publications, Ltd
• Subjects: Action Potentials; Animal behavior; Animal biology; Animals; Aversion; Behavior, Animal; Brain; Dopamine; Electroencephalography; Escape behavior; Escape Reaction; Experiments; Feet; Footshock; GABA; Glutamatergic transmission; Graphs; Habenula; Habenula - physiology; Hypothalamus (lateral); Hypothalamus - physiology; in vivo physiology; Laboratories; Life Sciences; Luteinizing hormone; Male; Mesencephalon; Mice, Inbred C57BL; Neural circuitry; Neural networks; Neural Pathways; Neurons; Neuroscience; Neurosciences; Shock; Short Report; γ-Aminobutyric acid; France; United Kingdom; aversion; mouse; habenula; in vivo physiology; neuroscience
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/eLife.30697

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.