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

Tchenio, Anna; Lecca, Salvatore; Valentinova, Kristina; Mameli, Manuel · Nat Commun · 2017

basic_science · Level V

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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 GABA<sub>B</sub>-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.

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