Limiting habenular hyperactivity ameliorates maternal separation-driven depressive-like symptoms. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Tchenio, Anna; Lecca, Salvatore; Valentinova, Kristina; Mameli, Manuel
• Is Part Of: Nature communications. Volume 8:Issue 1(2017)
• Page Start: 1
• Page End: 8
• Publication Date: 2017-12
• Subjects: Biology -- Periodicals; Physical sciences -- Periodicals; 505
• DOI: 10.1038/s41467-017-01192-1
• Languages: English
• ISSNs: 2041-1723

Abstract

Abstract 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. Early-life stress primes depression in adulthood. This study shows that early maternal separation leads to lateral habenula (LHb) hyperactivity and causes depressive-like phenotypes, the latter being reversible when LHb hyperactivity is reduced chemogenetically or through deep-brain stimulation.