The vomeronasal organ (VNO) projection pathway mediates the effects of pheromones on several essential psychosexual and neuroendocrine functions in a variety of vertebrate species. In preliminary studies with rats and mice we have used the immediate-early gene product, Fos, as a nuclear marker of neuronal activation in different segments of the VNO pathway. In both species the ability of odors from sexually active males to augment neuronal Fos in the VNO pathway was found to be sexually dimorphic. New studies are proposed to exploit the mouse as a model system in which to study pheromonal communication and to manipulate genes governing the development of the nervous system. These experiments will establish whether pheromones derived from male and female urine activate different populations of sensory neurons in the VNO epithelium which, in turn, project to different rostral-caudal subdivisions of the accessory olfactory bulb and whether these actions of urinary pheromones on neuronal Fos in the terminal regions (bed nucleus of the stria terminalis; medial preoptic area) of VNO pathway in male and female subjects and correlate these results with animals' preference to investigate these respective stimuli. The possible contribution of perinatal aromatization of testosterone to the male- typical organization of VNO-projection pathway function will be assessed by comparing urine-induced neuronal Fos responses and olfactory preferences in wild-type and transgenic mice with a null mutation of the CYP19 gene, which are aromatase deficient. A final study will determine whether the robust neuronal Fos responses to male urinary odors, normally present at all levels of the female's VNO pathway, are attenuated in the most central portion of this pathway in cycling females by the receipt of mating stimulation from the male. Such an effect of mating could explain the 'Bruce effect' in which urine from a strange male, but not from a familiar, recent mating partner, blocks the establishment of pregnancy. The results of these experiments should identify sites in a well-characterized anatomical pathway at which sex hormones and social experience affect the detection and/or processing of olfactory signals.
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