Scientists reveal how sexual experience causes changes in the brain’s internal state

Instinctive social behavior, especially sexual behavior, is the basis of individual survival and reproduction, so how does sexual experience cause changes in the internal state of the brain and affect instinctive behavior decisions? What are the key factors driving sexual satiety in both sexes?

Science recently published the latest progress of Li Ying’s team, a researcher at the Beijing Brain Science and Brain-like Research Center. After 3 years of research, they found that ejaculation is a key event that drives sexual satiety in both sexes, and for the first time discovered neural circuits in the striated bed nucleus (BNST) of the limbic system of mice that can continuously encode past sexual experiences, clarifying how sexual experiences affect mating motivation in animals of both sexes.

Li Ying told China Science News that this research can help us understand the neural mechanisms by which social experiences persist in the brain, and how this representation affects animal behavior in the long term.

Li Ying’s team Photo courtesy of interviewee

Sex and the brain

The brain is the body’s most complex organ, which converts various sensory information into different neural signals to regulate movement. This sensory-motor transition is closely related to the individual’s internal state and is empirically regulated. Social experience, especially sexual experience, can cause long-term changes in neural circuits related to social behavior and influence instinctive behaviors such as mating, fighting, and caring for pups.

In mice, male and female animals usually lose interest in mating and reach a state of sexual satiety after successful mating, and this change in internal state not only avoids the risk and wasted energy of finding a new mate, but is also critical to improving offspring reproduction rates. However, it is unclear whether there is a specific neural circuit-coding satiety state in the brains of both sexes, and how this coding influences individual behavioral choices in the long term.

“Rodent mice and humans are mammals with certain biological similarities, and we use mating behavior as an example to study how social experience leads to long-term changes in the internal state of the brain, which is important for understanding the neural basis of human social behavior.” Li Ang, co-first author of the paper and a doctoral student jointly trained by the Beijing Brain Science and Brain-like Research Center and Peking University, told reporters.

Through controlled experiments, the researchers first discovered that ejaculation is a key event that drives sexual satiety in both sexes, which selectively activates Esr2-expressing neurons in BNST (BNSTEsr2).

Calcium imaging in free-moving mice found that BNSTEsr2 neurons were specifically and strongly activated when ejaculation was felt in both male animals and when female animals felt ejaculation, compared to other types of neurons in this region, and did not respond significantly at other stages of mating.

Interestingly, after ejaculation, about half of BNSTEsr2 in both male and female mice remained intensified in spontaneous activity for a longer period of 15 to 30 minutes, suggesting that such neurons may continue to encode changes in the animal’s internal state after successful mating.

Li Ang told reporters that small microscope calcium imaging technology is a cutting-edge method to study the relationship between animal behavior and neuronal activity, and after implanting a lens in the mouse brain and imaging through a tiny microscope, you can clearly see the activity status of each neuron, “but through laboratory innovative technology, we have overcome the problem of low success rate of small microscope surgery in the past, and greatly improved the efficiency of experiments.” ”

A new perspective on research

In order to further investigate whether BNSTEsr2 neurons continue to encode individual satiety states, the researchers tracked the calcium activity of BNSTEsr2 neurons in mice of both sexes over a long period of time, and comprehensively compared the spontaneous activities of male and female mice at different stages of successful mating and before and after the recovery of mating motivation.

They found that mice of both sexes showed greater and higher frequency of spontaneous calcium activity only in the sexually satiety state and continued for several days throughout the sexual satiety period.

The researchers also found that in sexually saturated mice of both sexes, chemical genetic inhibition of BNSTEsr2 neuronal activity could restore their mating ability within 30 minutes; By Caspase3 selectively killing the BNSTEsr2 neurons of male mice, mice were able to mate for several days, that is, they could not reach sexual satiety.

Conversely, activating BNSTEsr2 neurons during the sniffing phase rather than after mating onset inhibits mating initiation in normal male mice, and these findings further suggest that BNSTEsr2 neurons play an important role in inhibiting mating motivation rather than mating action.

To understand the mechanism of persistent changes in BNSTEsr2 neural activity, the researchers recorded the electrophysiological properties of BNSTEsr2 neurons in amphoteric mice with asexual experience, sexual satiety, and mating ability to recover, using whole-cell patch-clamp methods. Experiments found that mice in a sexually saturated state exhibited higher excitability with more BNSTEsr2 neurons compared to mice with asexual experience and repaired mating ability.

Further studies found that BNSTEsr2 neurons in male mice in a sexually saturated state expressed more cyclic nucleotide gated channels (HCNs), which was not significant in female mice. Using CRISPR/Cas9 technology to selectively knock out the Hcn1 gene in BNSTEsr2 neurons, male mice showed significant loss of sexual satiety.

Li Ying said that this research covers many cutting-edge technologies in the field of neuroscience, and has made an important breakthrough in revealing the important scientific question of how sexual experience causes changes in the internal state of the brain, and also provides a new perspective for us to understand how sexual experience causes lasting changes in the brain.

But Li Ying also said that different social experiences can also cause long-term changes in other instinctive social behaviors, such as maternal behavior, fighting behavior, etc., “These changes are still very different in male and female mice, and it is not clear what the neural mechanism behind this is.” (Source: China Science News, Tian Ruiying)

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