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Authors Jennings Xu, Catherine Dulac, and Tali Kimchi

In rodents, as in most vertebrates, the social and sexual behaviors of males and females clearly differ. For example, female mice exhibit female-specific traits such as cycling sexual receptivity and strong maternal behavior, while male mice display male-specific courtship and sexual behavior.

What are the neural mechanisms that underlie these sexually dimorphic behaviors? For years, scientists have searched for identifiable anatomical differences in the female and male brains that may drive the dramatic sex-specific differences in behaviors. However, despite repeated attempts, the search for sex-specific brain structures or circuits has so far failed. Our recent study offers an alternative view on the nature of the control of sexually dimorphic behaviors.

In a set of experiments published in the August 5th issue of Nature (Kimchi, Xu, & Dulac, 2007) we have shown that the vomeronasal organ (VNO), an olfactory sensory organ in the nasal cavity of many mammals (although not in humans nor in higher primates) which detects pheromones, is responsible for the control of male- and female-specific social and sexual behaviors.

We discovered to our initial great astonishment, while observing the behavior of female mice in which the VNO has been genetically (Trpc2– knockout) or surgically (VNOx) inactivated, that they engage in male-typical courtship and sexual behaviors that is indistinguishable from that of normal male mice. Trpc2-/- and VNOx females vigorously chased the males, lifting and sniffing the males’ hindquarters with their snouts, singing to the males and, most amazingly, repeatedly attempted to mount the males. Furthermore, VNOx and Trpc2-/- females failed to distinguish between males and females and exhibited male-typical traits toward both sexes. Moreover, the VNO deficient females behaved as very bad mothers with diminished nursing behaviors and low level of maternal defense.

From this data a model emerges that provides a novel hypothesis for the neural control of social and sexual behavior in the mouse. Our findings suggest that pheromone inputs act in wild-type females to repress male specific behaviors and to activate female specific behaviors. This implies that the female brain contains structures and circuits underlying both female (as well as male) specific social and sexual displays. This model raises the intriguing hypothesis that, similarly, pheromones in males could specifically inhibit the activity of female-specific centers, and activate male-specific nuclei. Our next goal: to test Trpc2-/- males to try to identify a possible female circuit hidden and repressed inside male mouse brains.

What about other animal species and humans? Can this model be used to explain what factors determine sex-specific behaviors in humans and other animal species? Human beings do not have a functional Trpc2 gene or vomeronasal organ and, unlike mice, they rely mainly on visual cues for social communication. Our model can perhaps offer a fresh perspective and experimental paradigm for the study of social behavior in humans and other species.

Article in The Harvard Gazette
For Harvard Community: full text of article in Nature

View Catherine Dulac’s Faculty Profile