Messing with mouse brains during sex leads to unexpected discovery

Sex comprises an intricate tangle of impulses and interactions between partners. All the while, the brain hosts an even more complex tangle of chemicals. Neuroscientists have learned a great deal about the neural mechanisms underlying sex, but questions about the processes that control the sequence of events during sex remain unanswered.

While past research has identified the regions of the brain that control how mice initiate sex, other steps of copulation are still mysteries. A team of researchers in China and Japan have investigated which brain regions and neurotransmitters are responsible for different phases during sex. A paper published March 19 in the journal Neuron describes what exactly goes on in a mouse brain during sex. 

The paper specifically demonstrates what goes on in the male mouse brain while engaging in sex. “Through this study we understand how ejaculation is regulated in the brain,” says the paper’s first author Ai Miyasaka, a postdoctoral neuroscience researcher at the University of Tsukuba in Japan. Through studying neural activity in male mice during sex, Miyasaka and her team have identified two key neurotransmitters at play throughout the different stages of sex: dopamine and acetylcholine.

This finding demonstrates a concept that researchers had dismissed previously. “Neuroscientists didn’t believe that dopamine has a critical role in the regulation of ejaculation,” Miyasaka says. 

The pairing of dopamine and acetylcholine is the crux of the study. This paper represents a “landmark study that unravels the neural mechanisms governing sequential male sexual behaviors,” Changhe Wang, a professor of neuroscience at Xi’an Jiaotong University in China who was not involved in the study, explained in an email to Popular Science.

In particular, the chemical coupling underscores a major discovery. “The beauty of the paper is the tangle between dopamine and acetylcholine,” says Stephen Zhang, an assistant professor of neural science at New York University who was not involved in the study. It turns out this newly observed, dynamic tangle orchestrates the sequence of events that males perform during sex.

Dopamine figures into movement, memory, attention, and other functions, but is perhaps best associated with reward and good feelings. When a cool swig of water or a hearty meal makes you feel better, that’s dopamine rewarding you for surviving. Reproduction is also crucial to survival, so our brains evolved to make us feel good so we would reproduce more.

Acetylcholine plays a role in learning, attention, arousal, and other brain functions depending on what sorts of receptors it binds to, like a lock fitting into a key. Crucially, it also regulates dopamine.

In particular, the team looked at the dual roles of dopamine and acetylcholine in a part of the brain called the nucleus accumbens, which modulates action, motivation, and reward pathways. Within this structure, the team focused on an area called the ventral shell. 

The researchers used fiber photometry systems to detect neurotransmitters, which involved injecting the mice with fluorescent sensors. This injection revealed how the brain’s chemical messengers functioned in the nucleus accumbens during various stages of sex. Then, if the brain released dopamine and acetylcholine, an optic fiber would flash.

These systems revealed that in the male mouse brains, acetylcholine released rhythmically leading up to intromission—insertion of the penis into the vagina. During intromission, dopamine and acetylcholine would oscillate in the brain regularly with the mouse’s thrusting motions. In mice that ejaculated, dopamine release slowed significantly in the transition from intromission to ejaculation before rising quickly.

“I think it really is detangling the interplay between the dopamine and acetylcholine oscillation in this particular behavior context,” Zhang says. He’s especially intrigued that these oscillations are “phase-locked” to the behavior of the animal—that is, they’re generated within the context of specific stages of sex. “That, to me, is surprising and new and exciting.”

Analyzing activity of dopamine receptors also reinforced the role this neurotransmitter plays in changing stages of sexual behavior. Miyasaka and her team looked at D2R and D1R, two major dopamine receptors, during intromission. If the researcher artificially activated D1R receptors during this stage, the mice would move back to mounting. But if the researcher activated D2R, then the mice would stop entirely. This manipulation pinpoints the dopamine signaling mechanism that helps sexual behavior follow the correct sequence of events: mounting, intromission, and ejaculation.

This discovery could lead to potential sexual therapies. “This might contribute to the development of the clinical therapy for premature ejaculation,” Miyakasa says. Pharmaceutical applications could target dopamine release to regulate how the brain releases these neurotransmitters we now know are key to ejaculation.

However, Zhang sees a bigger picture. To him, this paper’s methodology speaks to greater neuroscience research potential. “The fact that we are able to record these signals, such as dopamine and acetylcholine, is important for the study of drug abuse or attention,” he says. “There are many, many different lines of insight.”

“I don’t see this as just a mating behavior study,” Zhang says. “It will inspire other studies that study the tangle between dopamine and acetylcholine.”

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