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A functional circuit underlying male sexual behaviour in the female mouse brain

Abstract

In mice, pheromone detection is mediated by the vomeronasal organ and the main olfactory epithelium. Male mice that are deficient for Trpc2, an ion channel specifically expressed in VNO neurons and essential for VNO sensory transduction, are impaired in sex discrimination and male–male aggression. We report here that Trpc2-/- female mice show a reduction in female-specific behaviour, including maternal aggression and lactating behaviour. Strikingly, mutant females display unique characteristics of male sexual and courtship behaviours such as mounting, pelvic thrust, solicitation, anogenital olfactory investigation, and emission of complex ultrasonic vocalizations towards male and female conspecific mice. The same behavioural phenotype is observed after VNO surgical removal in adult animals, and is not accompanied by disruption of the oestrous cycle and sex hormone levels. These findings suggest that VNO-mediated pheromone inputs act in wild-type females to repress male behaviour and activate female behaviours. Moreover, they imply that functional neuronal circuits underlying male-specific behaviours exist in the normal female mouse brain.

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Figure 1: Male-like sexual and courtship behaviours are displayed by Trpc2 -/- and VNOx females.
Figure 2: Ultrasonic vocalization by male and female mice in resident-intruder assays.
Figure 3: Surgery leads to a complete removal of the vomeronasal organ (VNOx) while the nasal airways stay clear.
Figure 4: Social behaviour of Trpc2 +/- and Trpc2 -/- females in semi-natural conditions.
Figure 5: Sexual dimorphic traits in Trpc2 -/- mutants and regulation of sexually dimorphic behaviour.

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Acknowledgements

We thank R. Hellmiss for artistic work and illustrations, S. Sullivan for assistance with behavioural analysis, A. E. Launjuin and S. Yao for help with histochemistry, the Dulac laboratory for discussions and comments on the manuscript, T. E. Holy, B. Ölveczky and A. Kampf for help with the recording of ultrasonic vocalizations. The work was supported by the Howard Hughes Medical Institute (to C.D.), the NIH (to C.D.) and the Human Frontier Science Program (to T.K.).

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Correspondence to Tali Kimchi or Catherine Dulac.

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Reprints and permissions information is available at www.nature.com/reprints. The authors declare no competing financial interests.

Supplementary information

Supplementary Information

This file contains Supplementary Figures S1-S4 with Legends and Supplementary Videos S1-S5 Legends. (PDF 933 kb)

Supplementary Video S1

This file contains Supplementary Video S1 showing TRPC2-/- female with intruder C57BL/6J female (MOV 4049 kb)

Supplementary Video S2

This file contains Supplementary Video S2 showing TRPC2-/- female with intruder C57BL/6J male. (MOV 5255 kb)

Supplementary Video S3

This file contains Supplementary Video S3 showing VNOx female with intruder C57BL/6J male. (MOV 3655 kb)

Supplementary Video S4

This file contains Supplementary Video S4 showing TRPC2+/- females (N=4) with sexually experienced C57BL/6J males (N=2). (MOV 6163 kb)

Supplementary Video S5

This file contains Supplementary Video S5 showing TRPC2-/- females (N=4) with sexually experienced C57BL/6J males (N=2). (MOV 6557 kb)

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Kimchi, T., Xu, J. & Dulac, C. A functional circuit underlying male sexual behaviour in the female mouse brain. Nature 448, 1009–1014 (2007). https://doi.org/10.1038/nature06089

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