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TitleOrexin signaling in GABAergic lateral habenula neurons modulates aggressive behavior in male mice.
Publication TypeJournal Article
Year of Publication2020
AuthorsFlanigan, Meghan E., Hossein Aleyasin, Long Li, Joseph C Burnett, Kenny L. Chan, Katherine B. LeClair, Elizabeth K. Lucas, Bridget Matikainen-Ankney, Romain Durand- de Cuttoli, Aki Takahashi, Caroline Menard, Madeline L. Pfau, Sam A. Golden, Sylvain Bouchard, Erin S. Calipari, Eric J. Nestler, Ralph J. DiLeone, Akihiro Yamanaka, George W. Huntley, Roger L. Clem, and Scott J. Russo
JournalNat Neurosci
Volume23
Issue5
Pagination638-650
Date Published2020 05
ISSN1546-1726
KeywordsAggression, Animals, GABAergic Neurons, Habenula, Male, Mice, Orexins, Signal Transduction
Abstract

Heightened aggression is characteristic of multiple neuropsychiatric disorders and can have various negative effects on patients, their families and the public. Recent studies in humans and animals have implicated brain reward circuits in aggression and suggest that, in subsets of aggressive individuals, domination of subordinate social targets is reinforcing. In this study, we showed that, in male mice, orexin neurons in the lateral hypothalamus activated a small population of glutamic acid decarboxylase 2 (GAD2)-expressing neurons in the lateral habenula (LHb) via orexin receptor 2 (OxR2) and that activation of these GAD2 neurons promoted male-male aggression and conditioned place preference for aggression-paired contexts. Moreover, LHb GAD2 neurons were inhibitory within the LHb and dampened the activity of the LHb as a whole. These results suggest that the orexin system is important for the regulation of inter-male aggressive behavior and provide the first functional evidence of a local inhibitory circuit within the LHb.

DOI10.1038/s41593-020-0617-7
Alternate JournalNat Neurosci
PubMed ID32284606
PubMed Central IDPMC7195257
Grant ListDP1 DA048931 / DA / NIDA NIH HHS / United States
R00 DA045662 / DA / NIDA NIH HHS / United States
R00 DA042111 / DA / NIDA NIH HHS / United States
R01 MH105414 / MH / NIMH NIH HHS / United States
R01 MH116445 / MH / NIMH NIH HHS / United States
R21 MH114170 / MH / NIMH NIH HHS / United States
K99 DA045662 / DA / NIDA NIH HHS / United States
R01 MH114882 / MH / NIMH NIH HHS / United States
R01 MH090264 / MH / NIMH NIH HHS / United States