Lateral habenula glutamatergic neurons projecting to the dorsal raphe nucleus promote aggressive arousal in mice

Aki Takahashi, Romain Durand-de Cuttoli, Meghan E. Flanigan, Emi Hasegawa, Tomomi Tsunematsu, Hossein Aleyasin, Yoan Cherasse, Ken Miya, Takuya Okada, Kazuko Keino-Masu, Koshiro Mitsui, Long Li, Vishwendra Patel, Robert D. Blitzer, Michael Lazarus, Kenji F. Tanaka, Akihiro Yamanaka, Takeshi Sakurai, Sonoko Ogawa, Scott J. Russo

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)


The dorsal raphe nucleus (DRN) is known to control aggressive behavior in mice. Here, we found that glutamatergic projections from the lateral habenula (LHb) to the DRN were activated in male mice that experienced pre-exposure to a rival male mouse (“social instigation”) resulting in heightened intermale aggression. Both chemogenetic and optogenetic suppression of the LHb-DRN projection blocked heightened aggression after social instigation in male mice. In contrast, inhibition of this pathway did not affect basal levels of aggressive behavior, suggesting that the activity of the LHb-DRN projection is not necessary for the expression of species-typical aggressive behavior, but required for the increase of aggressive behavior resulting from social instigation. Anatomical analysis showed that LHb neurons synapse on non-serotonergic DRN neurons that project to the ventral tegmental area (VTA), and optogenetic activation of the DRN-VTA projection increased aggressive behaviors. Our results demonstrate that the LHb glutamatergic inputs to the DRN promote aggressive arousal induced by social instigation, which contributes to aggressive behavior by activating VTA-projecting non-serotonergic DRN neurons as one of its potential targets.

Original languageEnglish
Article number4039
JournalNature communications
Issue number1
Publication statusPublished - 2022 Dec

ASJC Scopus subject areas

  • General Physics and Astronomy
  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology


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