While the VMHvl is unequivocally linked to female sexual receptivity, recent studies have uncovered an unappreciated complexity and multifunctional nature of this region, especially across its anterior posterior axis. In fact, it has been shown that receptivity is controlled by its most posterior region, as well as maternal aggression, in a hormone dependent manner. The rejection of sexual attempts should however not be mistaken for aggression but rather as a form of self-defense to avoid unwanted social interactions. Interestingly, rejection behavior displayed in the sexual context by female mice resembles the behavior of submissive males when faced with dominant intruders. Importantly, in males this self-defense behavior is controlled by the most anterior part of the VMHvl and as such we hypothesized if the anterior region of the VMHvl in females, in particular its PR+.VMHvl population, could be involved in rejection behavior when non-sexually receptive.
During the duration of this project, we gathered evidence supporting this hypothesis. In particular we have shown that:
- Anterior PR+VMHvl neurons are more active when non-receptive females interact with a male, an interaction dominated by rejection behavior, when compared with the same population in receptive females.
- Using calcium sensors to monitor the activity of PR+.VMHvl neurons in real time in behaving females, we found spatial segregation in the response profile of this population: while receptivity-related activity was observed in the posterior region, the anterior subpopulation is active when the female rejects.
- We have found a possible mechanism linking the reproductive cycle and the changing properties of anterior PR+.VMHvl neurons. With in vitro recordings we have found that the amount of inhibition received by anterior PR+.VMHvl neurons changes across the cycle, with these cells receiving less inhibition when females are non-fertile/non-receptive. This change in the amount of inhibition suggests that these cells might be more active when a non-receptive female interacts with a male and rejects him.
- To causally relate the changes in the electrophysiological properties of the anterior PR+.VMHvl population and rejection behavior, we performed optogenetic stimulation of anterior PR+.VMHvl neurons in receptive females which usually exhibit very low levels of rejection. As expected, the artificial stimulation increased rejection behavior in sexually receptive females and disrupted sexual behavior. Importantly, the behavior exhibited by manipulated females closely resembles the behavior of non-receptive females, supporting the idea that our manipulation impinged on the population that normally controls this behavior when females are not fertile.
- We have uncovered the output connectivity of the anterior and posterior PR+.VMHvl subpopulations to the midbrain, showing that anterior and posterior neurons have different connectivity, which might underlie the control of disparate behaviors, such as receptive posture and rejection.
