The vomeronasal organ (VNO) projection pathway mediates many of the effects of pheromones on essential psychosexual and neuroendocrine functions in a variety of vertebrate species. We have shown that different populations of neurons in the VNO of male and female mice respond to pheromones derived from male and female conspecifics and that estradiol and testosterone amplify these effects. Experiments are proposed to extend these findings by determining whether sex differences exist in the expression within the basal zone of the VNO of any three different V2R receptors previously cloned in mice, and whether any such differences in mRNA levels for these receptors are modulated by estradiol or testosterone. We will see whether the ability of male pheromones to augment Fos-IR in mitral cells that project to medial amygdaloid nuclei from the rostral as opposed to the caudal AOB differs in gonadectomized, estrogen-treated male and female mice and will use cellular compartment analysis of temporal activity by fluorescent in situ hybridization (catFISH) for the immediate-early-gene (IEG), c-fos, to determine whether mitral cells in the rostral versus caudal zones of the AOB are differentially activated by pheromones from male versus estrous female mice. Finally, we will determine whether the inhibition of male pheromone-induced IEG activation previously seen in the VNO of females two days after mating also occurs in male mice and in response to pheromones from both sexes, and we will assess the possible role of noradrenergic afferents from the superior cervical ganglia on the mating-induced 'silencing' of subsequent odor-induced IEG activation in the VNO. The results obtained in these studies should improve our understanding of the neurobiological mechanisms that underlie the effects of gender, steroid hormones, and previous coital experience on the processing of olfactory signals by the accessory olfactory system.