Previous research suggests that volatile body odourants detected by the main olfactory epithelium (MOE) are processed mainly by the main olfactory bulb (MOB) whereas nonvolatile body odourants detected by the vomeronasal organ (VNO) are processed via the accessory olfactory bulb (AOB). We asked whether urinary volatiles from males and females differentially activate the AOB in addition to the MOB in gonadectomized mice of either sex. Exposure to urinary volatiles from opposite-sex but not same-sex conspecifics augmented the number of Fos-immunoreactive mitral and granule cells in the AOB. Volatile urinary odours from male as well as female mice also stimulated Fos expression in distinct clusters of MOB glomeruli in both sexes. Intranasal administration of ZnSO 4 , intended to disrupt MOE function, eliminated the ability of volatile urinary odours to stimulate Fos in both the MOB and AOB. In ovariectomized, ZnSO 4 -treated females a significant, though attenuated, AOB Fos response occurred after direct nasal exposure to male urine plus soiled bedding, suggesting that VNO signaling remained partially functional in these mice. Future studies will determine whether MOE or VNO signaling, or both types of input, drive the sexually dimorphic response of the AOB to volatile opposite-sex odours and whether this AOB response contributes to reproductive success.

It was recently reported that female mice lacking a functional vomeronasal organ (VNO) displayed male-typical sexual behavior indiscriminately toward female and male conspecifics. These results have been cited as showing that a circuit controlling male-typical sex behavior exists in both sexes, with its activation in females being tonically inhibited by VNO signaling, independent of adult sex hormones. We further assessed this hypothesis while controlling the endocrine status of female mice in which VNO function was surgically disrupted. In experiment 1, VNO-lesioned (VNOx) female mice showed no more mounting or pelvic-thrusting behavior toward an estrous female or a castrated, urine-swabbed male (presented simultaneously) than sham-operated (VNOi) females. This was true when subjects were either ovary-intact or ovariectomized and treated with estradiol, estradiol plus progesterone, or testosterone. In experiment 2, female mice given accessory olfactory bulb lesions or a sham lesion displayed equivalent frequencies of male sex behaviors when given testosterone after ovariectomy. In experiment 3, VNOx and VNOi females displayed equivalent frequencies of male sex behaviors toward an estrous female or a castrated male (presented in separate tests), again, when given testosterone after ovariectomy. Our results confirm early reports that adult testosterone can stimulate appreciable male-typical sex behavior in female mice. However, we failed to corroborate the recent claim that VNO signaling normally inhibits the activity of neural circuitry controlling the expression of male-typical mating behavior by female mice.

We previously found that female mice exhibited Fos responses in the accessory olfactory bulb (AOB) after exposure to volatile opposite-, but not same-sex, urinary odours. This effect was eliminated by lesioning the main olfactory epithelium, raising the possibility that the AOB receives information about gender via centrifugal inputs originating in the main olfactory system instead of from the vomeronasal organ. We asked which main olfactory forebrain targets send axonal projections to the AOB, and whether these input neurons express Fos in response to opposite-sex urinary volatiles. Female mice received bilateral injections of the retrograde tracer, cholera toxin B (CTB), into the AOB, and were exposed to either same-or opposite-sex volatile urinary odours one week later. We found CTB-labeled cell bodies in several forebrain sites including the bed nucleus of the accessory olfactory tract, the rostral portion of the medial amygdala (MeA), and the posteromedial cortical nucleus of the amygdala. A significant increase in the percentage of CTB/Fos co-labeled cells was seen only in the MeA of female subjects exposed to male but not to female urinary volatiles. In Experiment 2, CTB-injected females were later exposed to volatile odours from male mouse urine, food, or cat urine. Again, a significant increase in the percentage of CTB/Fos co-labeled cells was seen in the MeA of females exposed to male mouse urinary volatiles but not to food or predator odours. Main olfactory -MeA -AOB signaling may motivate approach behaviour to opposite-sex pheromonal signals that ensure successful reproduction.

Previously [D.W. Wesson, M. Keller, Q. Douhard, M.J. Baum, J. Bakker, Enhanced urinary odor discrimination in female aromatase knockout mice, Horm. Behav. 49 (2006) [580][581][582][583][584][585][586] female aromatase knock out mice successfully learned to discriminate in a food-motivated go/no-go task between urinary volatiles from ovariectomized female mice treated with estradiol as opposed to estradiol plus progesterone whereas wild type females failed to learn this odor discrimination. We asked whether this behavioral difference is reflected in the ability of these two types of urinary volatiles to differentially stimulate Fos expression in juxtaglomerular cells (an index of glomerular activation) of the main olfactory bulb (MOB) in wild type versus ArKO female mice. Statistically significant differences in the profiles of MOB glomerular activation were seen in ovariectomized, estrogen-treated ArKO as well as WT female subjects following exposure to urinary volatiles from ovariectomized females given estradiol alone as opposed to estradiol plus progesterone. Therefore, previously observed differences between females of the two genotypes in their behavioral responses to these odors must reflect differential processing in more central segments of the olfactory pathway instead of in the MOB. © 2007 Elsevier Ireland Ltd. All rights reserved.Keywords: Estradiol; Progesterone; Pheromone; Sexual differentiation; Fos expression Olfactory receptor neurons in the main olfactory epithelium (MOE) that express the same olfactory receptor gene extend axons that target the same 1-2 glomeruli in the ipsilateral main olfactory bulb (MOB) [10]. Recently [6] a class of 'trace amineassociated receptors' was identified in the MOE which respond to volatile amines emitted from mouse urine. A series of studies by Restrepo and co-workers [13,12,7] showed that volatile urinary odors from male mice augmented Fos expression in juxtaglomerular cells of the MOB (an index of glomerular activation) of female conspecifics. More recently, Martel and Baum [9] used this same method to show that urinary volatiles from male versus estrous female mice activated overlapping, but distinguishable clusters of glomeruli located in the ventral portion of the MOB in both sexes. In another study [8] volatile constituents of mouse urine were shown to stimulate activity in MOB mitral cells. Wesson et al. [14] recently assessed the possible contribution of perinatal exposure to estradiol on the later ability of female mice to discriminate volatile urinary odors from * Corresponding author. conspecifics of different sexes and endocrine status. Detection of these social odorants plays a significant role in sexual, aggressive, and maternal behaviors in mice, therefore the possible role of perinatal estradiol exposure on the later ability of female mice to discriminate between urinary odors of conspecifics is of particular interest. Female mice with a null mutation of the Cyp-19 gene (ArKO mice), which encodes the estradiol synthesizing enzyme, aroma...