Esr1+ cells in the ventromedial hypothalamus control female aggression

  • Koichi Hashikawa
  • , Yoshiko Hashikawa
  • , Robin Tremblay
  • , Jiaxing Zhang
  • , James E. Feng
  • , Alexander Sabol
  • , Walter T. Piper
  • , Hyosang Lee
  • , Bernardo Rudy
  • , Dayu Lin

Research output: Contribution to journalArticlepeer-review

203 Scopus citations

Abstract

As an essential means of resolving conflicts, aggression is expressed by both sexes but often at a higher level in males than in females. Recent studies suggest that cells in the ventrolateral part of the ventromedial hypothalamus (VMHvl) that express estrogen receptor-α (Esr1) and progesterone receptor are essential for male but not female mouse aggression. In contrast, here we show that VMHvl Esr1+ cells are indispensable for female aggression. This population was active when females attacked naturally. Inactivation of these cells reduced female aggression whereas their activation elicited attack. Additionally, we found that female VMHvl contains two anatomically distinguishable subdivisions that showed differential gene expression, projection and activation patterns after mating and fighting. These results support an essential role of the VMHvl in both male and female aggression and reveal the existence of two previously unappreciated subdivisions in the female VMHvl that are involved in distinct social behaviors.

Original languageEnglish
Pages (from-to)1580-1590
Number of pages11
JournalNature Neuroscience
Volume20
Issue number11
DOIs
StatePublished - 2017

Bibliographical note

Funding Information:
We thank D. Anderson (California Institute of Technology) for providing Esr1-2A-Cre mice and B. Lowell (Harvard Medical School) for providing Vglut2-ires-Cre and Vgat-ires-Cre mice and AAV-DIO-synaptophysin-mCherry for the pilot experiments. We thank R. Machold and M. Baek for technical support on in situ hybridization and RNA-seq, C. Loomis at the NYULMC Experimental Pathology Research Laboratory for help on laser capture microdissection, A. Heguy and Y. Zhang at the NYULMC Genome Technology Center for help on RNA-seq and T. Lhakhang at the NYULMC Bioinformatics Laboratory for help with sequence alignment. We thank A.L. Falkner, M. Halassa, G. Stuber and G. Suh for critical comments on the manuscript. This research was supported by a JSPS oversea fellowship (K.H.), Uehara postdoctoral fellowship (K.H.), National Natural Science Foundation of China 81471630 (J.Z.), NIH 1K99NS074077 (H.L.), NIH R21NS093987 (B.R.), NIH P01NS074972 (B.R.), NIH 1R01MH101377 (D. L.), NIH 1R21MH105774-01A1 (D. L.), the Mathers Foundation (D.L.), an Irma T. Hirschl Career Scientist Award (D.L.), a Sloan Research Fellowship (D.L.), a McKnight Scholar Award (D.L.), a Whitehall Fellowship (D.L.) and a Klingenstein Fellowship Award (D.L.).

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