Limiting habenular hyperactivity ameliorates maternal separation-driven depressive-like symptoms

Nat Commun. 2017 Oct 26;8(1):1135. doi: 10.1038/s41467-017-01192-1.


Early-life stress, including maternal separation (MS), increases the vulnerability to develop mood disorders later in life, but the underlying mechanisms remain elusive. We report that MS promotes depressive-like symptoms in mice at a mature stage of life. Along with this behavioral phenotype, MS drives reduction of GABAB-GIRK signaling and the subsequent lateral habenula (LHb) hyperexcitability-an anatomical substrate devoted to aversive encoding. Attenuating LHb hyperactivity using chemogenetic tools and deep-brain stimulation ameliorates MS depressive-like symptoms. This provides insights on mechanisms and strategies to alleviate stress-dependent affective behaviors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Deep Brain Stimulation
  • Depression / physiopathology*
  • Depression / psychology
  • Depression / therapy
  • Female
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels / physiology
  • Habenula / physiopathology*
  • Male
  • Maternal Deprivation*
  • Mice, Inbred C57BL
  • Receptors, GABA-B / physiology
  • Signal Transduction / physiology
  • Stress, Psychological / physiopathology*
  • Stress, Psychological / psychology
  • Stress, Psychological / therapy
  • Synaptic Transmission / physiology


  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • Receptors, GABA-B