The roles of the main and accessory olfactory systems in the detection of social odors in mice

Our understanding of olfaction has been built on the study of monomolecular (pure) odors, which are easily obtained and well characterized chemically. For most species social odors have far greater biological relevance than typical monomolecular odors, but much less is known about the neural circuits that process them. Three studies were conducted to further explore the neural pathways that process social odors in mice. In Study 1, a Go-No-Go olfactory discrimination task was used to ask whether social odors are more salient stimuli than non-social odors in males and females under different hormonal conditions. Performance (percent correct) was greater in males than females, and poorer in subjects without circulating gonadal hormones when mice were required to discriminate between two social odors (male versus female urine), but not when non-social odors (banana versus peppermint) were used. This suggests that social odors are more salient stimuli than non-social odors but only when gonadal hormones are present. The piriform cortex (PC) is the primary cortical target for volatile odors processed by the main olfactory system (MOS); whether the PC responds to social odor volatiles is not known. In Study 2 I recorded extracellularly from PC pyramidal neurons before and during exposure to urinary volatiles or amyl acetate (banana) in anesthetized males. Neuronal spiking was strongly dependent on testosterone levels. Notably, social odor exposure only weakly induced spiking, which contrasts with the strong behavioral effects these odors are known to induce, so it is likely that other, unknown pathways are more important for their detection. Non-volatile components of social odors are processed by the accessory olfactory system (AOS); however, the role of the AOS during ongoing social interactions is not clear. In Study 3 I used optogenetic activation of the AOB during mating to enhance signaling in the AOS of males; I found that this stimulation significantly increased copulatory behavior efficiency, suggesting that AOB activity during mating facilitates males’ sexual arousal and reproductive performance. Overall these results reveal new properties of social odor processing in mice: sex differences, dependence on gonadal hormones, and a role during ongoing behavioral interactions

Optogenetic activation of accessory olfactory bulb input to the forebrain differentially modulates investigation of opposite versus same-sex urinary chemosignals and stimulates mating in male mice

Surgical or genetic disruption of vomeronasal organ (VNO)-accessory olfactory bulb (AOB) function previously eliminated the ability of male mice to processes pheromones that elicit territorial behavior and aggression. By contrast, neither disruption significantly affected mating behaviors, although VNO lesions reduced males' investigation of nonvolatile female pheromones. We explored the contribution of VNO-AOB pheromonal processing to male courtship using optogenetic activation of AOB projections to the forebrain. Protocadherin-Cre male transgenic mice received bilateral AOB infections with channelrhodopsin2 (ChR2) viral vectors, and an optical fiber was implanted above the AOB. In olfactory choice tests, males preferred estrous female urine (EFU) over water; however, this preference was eliminated when diluted (5%) EFU was substituted for 100% EFU. Optogenetic AOB activation concurrent with nasal contact significantly augmented males' investigation compared to 5% EFU alone. Conversely, concurrent optogenetic AOB activation significantly reduced males' nasal investigation of diluted urine from gonadally intact males (5% IMU) compared to 5% IMU alone. These divergent effects of AOB optogenetic activation were lost when males were prevented from making direct nasal contact. Optogenetic AOB stimulation also failed to augment males' nasal investigation of deionized water or of food odors. Finally, during mating tests, optogenetic AOB stimulation delivered for 30 s when the male was in physical contact with an estrous female significantly facilitated the occurrence of penile intromission. Our results suggest that VNO-AOB signaling differentially modifies males' motivation to seek out female vs male urinary pheromones while augmenting males' sexual arousal leading to intromission and improved reproductive performance