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 non-volatile 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 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 seconds 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.
Significance Statement The vomeronasal organ (VNO) – accessory olfactory bulb (AOB) pathway forms a pheromone processing circuit that controls social behaviors of mice. Here, optogenetic activation of AOB forebrain projections increased males’ nasal investigation of diluted (5%) estrous female urine but reduced males’ investigation of diluted (5%) testes-intact male urine. No effects of AOB optogenetic activation were seen when paired with nasal access to either water alone or diluted food odors, or when urinary volatiles alone were present. AOB optogenetic activation also augmented males’ capacity for penile intromission with an estrous female. These findings extend prior studies suggesting that the accessory olfactory system motivates male mice to seek out opposite-sex and avoid same-sex pheromones while augmenting sexual arousal and resultant reproductive performance.
The authors declare no competing financial interests.
This work was supported by NIH grant DC008962 awarded to JAC.