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

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

Tchenio A1,2,3,4, Lecca S1,2,3,4, Valentinova K1,2,3,4, Mameli M5,6,7,8.

Author information

1
Institut du Fer à Moulin, Paris, 75005, France.
2
Inserm, UMR-S 839, Paris, 75005, France.
3
Université Pierre et Marie Curie, Paris, 75005, France.
4
Department of Fundamental Neuroscience, The University of Lausanne, Lausanne, 1005, Switzerland.
5
Institut du Fer à Moulin, Paris, 75005, France. manuel.mameli@unil.ch.
6
Inserm, UMR-S 839, Paris, 75005, France. manuel.mameli@unil.ch.
7
Université Pierre et Marie Curie, Paris, 75005, France. manuel.mameli@unil.ch.
8
Department of Fundamental Neuroscience, The University of Lausanne, Lausanne, 1005, Switzerland. manuel.mameli@unil.ch.

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.

PMID:
29074844
PMCID:
PMC5658350
DOI:
10.1038/s41467-017-01192-1
[Indexed for MEDLINE]
Free PMC Article

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