Department of Molecular and Cellular Biology
Dept. of Molecular & Cellular Biology
16 Divinity Avenue, BL 4017
Cambridge, MA 02138
My laboratory is exploring the molecular logic of olfactory and pheromone signaling underlying specific behavioral responses, and is interested in identifying developmental processes that ensure the appropriate specification of distinct chemosensory neuronal populations within the nasal cavity.
Pheromones have evolved in all animal phyla, including mammals, to signal the sex and the dominance status of animals and to promote mating and social rituals among conspecifics. In mammals, the olfactory system has classically been presented as a dual structure, both anatomically and functionally, in which pheromones detection occurs primarily in the vomeronasal organ (VNO), an olfactory structure apposed to the ventral nasal septum, while volatile odorants are detected by the main olfactory epithelium (MOE). The ability to associate chemosensory stimulation with specific behavioral outputs and defined hormone changes provides a unique opportunity to uncover the neural basis of mammalian behavior.
Work performed in my laboratory has been instrumental in identifying novel families of candidate pheromone receptors, V1Rs and V2Rs, as well as signal transduction components unique to the VNO (reviewed in Dulac and Torello 2003). The genetic ablation of TRPC2 led to a direct assessment of the role of the VNO in pheromonemediated behaviors (Stowers et al., 2002, Leypold et al., 2002). We found that TRPC2 deficiency eliminates the sensory activation of VNO neurons by urine pheromones. Moreover, TRPC2–/– male mice fail to display the pheromone-evoked aggression toward male intruders that is normally seen in wild-type males, and display courtship and mounting behavior indiscriminately toward both males and females. These data contradicted the established notion that VNO activity is required for the initiation of male-female mating behavior in the mouse and suggested instead a critical role in ensuring sex discrimination.
More recently, we have reported that TRPC2-/- female mice show loss of sex discrimination and reduction in female-specific behavior, which includes maternal aggression and lactating behavior (Kimchi et al., 2007). Most strikingly, mutant females display unique characteristics of male sexual and courtship behaviors such as mounting, pelvic thrust, solicitation, anogenital olfactory investigation, and emission of complex ultrasonic vocalizations. The same behavioral phenotype is observed after VNO surgical removal in adult animals, and is not accompanied by disruption of the estrous cycle and sex hormone levels. These findings suggest that VNO-mediated pheromone inputs act in wild-type females to repress male behavior and activate female behaviors. Moreover, they imply that functional neuronal circuits underlying male-specific behaviors exist in the normal female mouse brain.
Our future projects will aim to identify and decipher the mechanism of action of circuits underlying social behavior using molecular and genetic tools.
Kimchi, T., Xu, J. and Dulac, C. (2007) A functional circuit underlying male sexual behaviour in the female mouse brain. Nature 448:1009-1014.
Yoon H, L. W. Enquist and Dulac C. (2005) Olfactory inputs to hypothalamic neurons controlling reproduction and fertility. Cell, 123, 669-682.
Tietjen, I., Rihel, J., Cao, Y., Zachary, L. and Dulac, C., (2003). Single-cell transcriptional analysis of neuronal progenitors. Neuron 38: 161-175.
Loconto, J., Papes, F., Chang, E., Stowers, L., Jones, E., Takada, T., Kumanovics, A., Fisher-Lindahl, K., and Dulac, C., (2002). Functional Expression of Murine V2R Pheromone Receptors Involves Selective Association with the M10 and M1 Families of MHC Class Ib Molecules. Cell 2003 112: 607-618.
Stowers, L., Holy, T., Meister, M., Dulac, C. and Koetnges, G. (2002). Loss of sex discrimination and male-male aggression in mice deficient in TRP2. Science, 295, 1493-1500.
For a complete listing of publications click here.
Last Update: 7/26/2012