The same brain circuit drives female desire and suppresses it in men

Scientists have found a significant paradox in the brain’s reproductive wiring: causing women to seek partners to actively dissuade the same neurons in men’s same behavior.

The discovery, published in the cell by researchers at Rockefeller University and Tsinghua University, reveals how individual brain circuits produce completely opposite behaviors based on biological gender, which can certainly explain the fundamental differences in reproductive drive between men and women.

“Hormone countries and biological genders can both flexibly carve this common tour to produce specific social behavior patterns,” explains Kun Li, senior co-author and associate professor at Tsinghua University. “This can help explain why sexual motivation and social interest fluctuates between reproductive states and differentiate between genders.”

Neural switches for reproductive drives

The team identified specific populations of neurons in the medial prefrontal cortex (MPFC) that expresses the CACNA1H gene. These neurons respond significantly to the “bonding hormone” oxytocin and estrogen (such as estrogen), which is essentially the point of integration between social signals and internal reproductive readiness.

In female mice, these neurons become highly active during the estrus (fertile period), driving them to seek male partners and exhibit accepted mating behaviors. When researchers artificially activate these neurons during a fertile period, the women start to appear as if hormones are mating, even if there is no hormone mating.

The most surprising finding was when checking the same circuits for men. The same neurons have the opposite effect – when activated, they greatly reduce male interest in females and inhibit mating behavior.

• In female mice, activation of these neurons increased interest in male guidance during estrus 47% during estrus
• Silence of the same neurons in males increases female-guided research and enhanced installation behavior
• Neurons respond differently to opposite sex cues according to gender: activated in women and inhibited in men
• Removal of the Cacna1h gene from the prefrontal cortex reverses these patterns in both genders

A cellular window for gender differences

The researchers observed these neurons using advanced calcium imaging techniques as mice interact with potential partners. In women, neurons have increased activity when studying males during estrus. In men, the same neurons showed reduced activity when studying women.

“This is interesting,” said study associate professor Ines Ibañez-Tallon, co-author of the study. “Even if the neural circuits, neuronal populations and molecular components are the same (only different at their expression levels), the system produces significantly different functional results.”

The tour’s activities explain a fundamental aspect of reproductive biology: women usually mated only during certain fertile periods, while men maintained a relatively consistent interest in mating. These biological differences appear to be rooted by the relative role of these prefrontal neurons.

Functions of hormone-shaping circuits

The researchers found that ovarian hormones dramatically alter the expression of the CACNA1H gene during estrus, thus changing the response of these neurons to social prompts. Specifically, hormone fluctuations modify the calcium channels encoded by CacNA1H, thereby enhancing the excitability of neurons during fertile periods.

This provides a molecular explanation for how the hormone cycle produces a reproductive reception window in women. When estrogen levels rise in estrogen, neurons become more active in response to male cues, driving social approaches to increase and reduce rejection behavior.

This circuit communicates with deeper brain regions (the pre-dehyalamic nucleus), a known structure that regulates basic drivers, including reproduction. This connection creates a pathway by which complex social judgments in the prefrontal cortex can influence instinctive reproductive behavior.

The study may ultimately help explain some patterns of sexual dysfunction in humans, including why deglycemia affects twice as many men, while patients have more than twice as sexual intercourse as commonly seen in men. Shared but functionally opposite circuits may represent an evolutionary solution to different reproductive strategies among genders.

Future research will explore how testosterone affects this circuit in men and that these findings may be related to gender differences in various neuropsychiatric disorders, which may open up new avenues to understand diseases that exhibit strong sexual bias.

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