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 VMHvlEsr1+ 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.
Access optionsAccess options
Subscribe to Journal
Get full journal access for 1 year
only $18.75 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Gene Expression Omnibus
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.).
Integrated supplementary information
The GCaMP6f signal of Esr1+ neurons in the VMHvl of a female mouse was recorded using fiber photometry. There was little change in GCaMP6f signal when the female investigated a toy mouse.
The VMHvl Esr1+ population in a virgin female responded during aggressive encounters with a juvenile male mouse.
GCaMP6f signal increased when the same female as shown in Supplementary Video 1 investigated or attacked a juvenile mouse.
The VMHvl Esr1+ population in a virgin SW female responded during a sexual interaction with an adult male mouse.
GCaMP6f signal increased when the same female as shown in Supplementary Video 1 investigated or was engaged in sexual intercourse with an adult male mouse.
The VMHvl Esr1+ population in a lactating SW female responded during aggressive encounters with an adult male mouse.
The GCaMP6f signal of Esr1+ neurons in the VMHvl of a lactating female mouse increased when the female attacked an adult male mouse.
Optogenetic activation of VMHvl Esr1+ neurons elicited social investigation of and attack on an adult female in a virgin SW female mouse.
A SW female mouse that expressed ChR2 in Esr1+ neurons of the VMHvl was photostimulated through an optic fiber at 0.1, 0.4 or 1.5 mW, 20 Hz, 20-ms pulses. Light-induced behaviors progressed from investigation to attack as the light intensity increased.
Optogenetic activation of VMHvl Esr1+ neurons elicited mounting towards an adult female and an adult male in a virgin C57 female mouse.
A C57 female mouse that expressed ChR2 in Esr1+ neurons of the VMHvl was photostimulated through an optic fiber at 20 Hz, 20 ms, 0.12 mW. The light induced mounting towards a female intruder, as well as a male intruder.
Optogenetic activation of VMHvl Esr1+ neurons elicited attack on an adult female in a lactating C57 female mouse.
A lactating C57 female mouse (postpartum day 3) that expressed ChR2 in Esr1+ neurons of the VMHvl was photostimulated through an optic fiber at 20 Hz, 20 ms, 0.35 mW. Light induced an attack on a female intruder.
The 3D reconstruction of fighting- and mating-related populations in the VMHvl at all bregma levels of a female mouse used in a Fos catFISH experiment. Red, blue, and yellow dots indicate cells activated by fighting, mating and both, respectively.
About this article
Nature Neuroscience (2018)