2. Academic Validation
  3. Orexin signaling in GABAergic lateral habenula neurons modulates aggressive behavior in male mice

Orexin signaling in GABAergic lateral habenula neurons modulates aggressive behavior in male mice

  • Nat Neurosci. 2020 May;23(5):638-650. doi: 10.1038/s41593-020-0617-7.
Meghan E Flanigan 1 2,  Hossein Aleyasin 1 2,  Long Li 1 2,  C Joseph Burnett 1 2,  Kenny L Chan 1 2,  Katherine B LeClair 1 2,  Elizabeth K Lucas 1 2 3,  Bridget Matikainen-Ankney 1 2,  Romain Durand-de Cuttoli 1 2,  Aki Takahashi 1 2 4,  Caroline Menard 1 2 5,  Madeline L Pfau 1 2,  Sam A Golden 6,  Sylvain Bouchard 1 2,  Erin S Calipari 1 2 7,  Eric J Nestler 1 2,  Ralph J DiLeone 8,  Akihiro Yamanaka 9,  George W Huntley 1 2,  Roger L Clem 1 2,  Scott J Russo 10 11
Affiliations

Affiliations

  • 1 Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 2 Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
  • 3 Department of Molecular Biomedical Sciences, North Carolina State University, Raleigh, NC, USA.
  • 4 Laboratory of Behavioral Neuroendocrinology, University of Tsukuba, Tsukuba, Ibaraki, Japan.
  • 5 Department of Psychiatry and Neuroscience, Faculty of Medicine and CERVO Brain Research Center, Université Laval, Ville de Québec, QC, Canada.
  • 6 Department of Biological Structure, University of Washington, Seattle, WA, USA.
  • 7 Department of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • 8 Department of Psychiatry, Yale University, New Haven, CT, USA.
  • 9 Department of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan.
  • 10 Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA. scott.russo@mssm.edu.
  • 11 Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. scott.russo@mssm.edu.
PMID: 32284606 DOI: 10.1038/s41593-020-0617-7
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.

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