Researchers at the Champalimaud Foundation (CF) have identified a neural circuit in the brain that governs sexual rejection in female mammals, providing key insights into the mechanisms shaping social and reproductive behaviors. Researchers from the Champalimaud Foundation have discovered a brain circuit that controls sexual rejection among female mammal species. This discovery provides important insights on the social and reproductive behavior of women.
The study reveals how a specific population of progesterone-sensitive neurons in the ventromedial hypothalamus (VMH) acts as a switch between acceptance and rejection of mating attempts based on a female's reproductive state. "Sexual rejection isn't just the absence of receptivity, it's an active behaviour", explains Susana Lima, senior author and head of the Neuroethology Lab at CF. Susana Lima is a senior author at CF and the head of their Neuroethology Lab. She explains that sexual rejection doesn't simply mean the lack of receptivity. It's an actively-motivated behaviour. "Females exhibit defensive actions like running away, kicking, or boxing the male. Females will often take defensive action against males, such as kicking or running away. We wanted to understand how the brain switches between these two drastically different behavioural states." "We wanted to know how the brain switched between these two dramatically different behaviour states."
The team honed in on the VMH, a brain region critical for social and reproductive behaviors, particularly its anterior section. This team focused on the VMH region, which is critical to social and reproductive behavior, especially its anterior part. These neurons, responsive to fluctuations in the hormone progesterone, were suspected of playing a role in switching between behavioral states. Using fibre photometry, a technique that measures real-time calcium signals in neurons, researchers observed stark differences in activity levels of progesterone-sensitive neurons in female mice during interactions with males. In non-receptive females, these neurons became highly active, correlating with rejection behaviors. These neurons are highly active in non-receptive women, which correlates with rejective behaviors. In contrast, their activity decreased during fertile phases, allowing mating to occur. Their activity was reduced during the fertile phase, which allowed for mating.
"It appears that progesterone-responsive neurons in the anterior VMH act as gatekeepers for sexual rejection", says co-first author Basma Husain. The team confirmed their role through optogenetics, a method that uses light to control neural activity. Optogenetics was used to confirm their function. This method uses light in order to regulate neural activity. Activating these neurons during the fertile phase triggered rejection behaviors, while silencing them in non-receptive females reduced rejection, though it did not induce full receptivity. Silencing these neurons in females who were not receptive reduced the rejection behavior, but did not increase it.
The research also highlighted the dual-system nature of behavioral control in the VMH. This research has also revealed the existence of a dual system for behavioral control within the VMH. While progesterone-sensitive neurons in the anterior VMH govern rejection, their counterparts in the posterior VMH regulate receptivity. These populations work in tandem, responding to the balance of excitatory and inhibitory signals based on a female's internal state. Both populations respond to excitatory or inhibitory signals depending on the internal state of a woman. "This setup gives the brain two 'knobs' to adjust", Lima explains. Lima says that this setup allows the brain to make adjustments with two knobs. "It's a more efficient and robust way for the brain to balance these behaviours, ensuring mating occurs when conception is most likely, while minimising the risks and costs of mating, such as exposure to predators or diseases". It's an efficient way to ensure mating happens when conception is likely while minimizing the costs and risks of mating such as being exposed to diseases or predators.
The study sheds light on how hormonal and neural mechanisms interact to shape behavior, offering potential insights into human health. This study provides new insights on the interaction between hormonal and neuronal mechanisms to influence behavior. It could also provide valuable information about human health. The VMH is present in humans and may play similar roles in regulating reproductive and social behaviors. VMH may also play a similar role in the regulation of social and reproductive behaviors. Abnormalities in this brain region have been linked to conditions such as polycystic ovarian syndrome and altered social behaviors stemming from early-life isolation. This brain area has been associated with conditions like polycystic kidney syndrome, and social behavior changes that result from childhood isolation. "Our findings underscore the VMH's clinical relevance," says Lima. Lima says that "our findings highlight the clinical relevance of VMH." "By understanding its role in normal and pathological conditions, we may uncover new pathways for addressing reproductive and social disorders."
Beyond reproductive behavior, the study opens the door to exploring how similar mechanisms might govern other complex social interactions. The study also opens up the possibility of exploring similar mechanisms that might be involved in other social interactions. "The VMH exists in humans and likely plays similar roles", notes Lima. Lima notes that "the VMH is present in humans, and it likely has similar functions". "Recent studies in mouse models have shown that the VMH changes in pathological conditions like polycystic ovarian syndrome. Recent studies on mouse models showed that VMH is altered in polycystic conditions such as polycystic syndrome. Additionally, socially isolating female mice during development may lead to reduced sexual receptivity, with alterations in the same brain area, underscoring the VMH's clinical relevance". The clinical significance of the VMH is also highlighted by the fact that socially isolated female mice may have a reduced sexual receptivity. This could be due to changes in the brain region responsible for this.
The study has been published in Neuron. Neuron has published the study.