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

Elife. 2017 Sep 5;6:e30697. 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.

Keywords: aversion; habenula; in vivo physiology; mouse; neuroscience.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials
  • Animals
  • Behavior, Animal*
  • Electroencephalography
  • Escape Reaction*
  • Habenula / physiology*
  • Hypothalamus / physiology*
  • Male
  • Mice, Inbred C57BL
  • Neural Pathways*

Grant support

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.