Scientists mapped the brain circuitry involved in pleasurable touch in mice

In 2018, when Leah Elias was a behavioral neuroscience graduate student at the University of Pennsylvania, she noticed something unusual while stimulating nerves in a mouse’s back. The mouse was curving her back... suggestively.

Elias, now a postdoctoral neuroscience fellow at Johns Hopkins University, knew a “sexually receptive posture” in a mouse when she saw one. The question was: What was it about those nerves that elicited such a recognizable pose?

Touch is elemental to existence. And yet, researchers still puzzle over the underlying neural mechanisms. Mammals, including humans, have nerve receptors in their skin called C tactile afferents that respond to gentle, nonpainful contact. But we still don’t know what happens after those receptors are stimulated. What path in the brain does the electrical impulse take? A new study in mice might help us get there.

A paper published early this month in the journal Cell on a mouse model brings us a step closer to understanding that instantaneous jolt from the skin to the brain when someone grazes our skin. Researchers from the Zuckerman Mind Brain Behavior Institute, including Elias, explored the relationship between a certain group of cells in the brain and a positive response to gentle touch.

What’s new — The new study attempts to map the skin-to-brain neural highway that occurs during gentle touch.

Neuroscientists have been making progress on this connection for years. A 2021 paper from Harvard identified one piece of the highway: GPR83 cells in the spinal cord. When it comes to the sensation of touch, activated nerve endings in the skin send signals zipping through the spinal cord and up to the brain, where we perceive the feeling created. Particularly, it’s GPR83 cells in the spinal cord that register and direct the stimulus from what’s known as affective touch or gentle stroking. This new paper provides new information that could create a more complete understanding of that circuit.

The researchers in the new study narrowed in on a group of cells called Mrgprb4 cells in the brain. They already knew that these cells detect mechanical stimulation, which is useful when feeling around for a particular object one can’t see, but the new study suggests both Mrgprb4 cells and GPR83 cells play a specific role in sensitive touch, too. They’re also the analog to C tactile afferents in humans, which made them a prime target for this study.

Digging into the details — To understand how specific types of cells influence behavior, the team used a technique known as optogenetics. This method entails modifying those cells, in this case, Mrgprb4, when a colored light shines on them. According to their hypothesis that these cells are involved in pleasurable touch, using a light to activate Mrgprb4 would trigger a reward area in the brain.

Pleasant touch stimulates the reward area in the brain because the feel-good chemical dopamine is released into the nucleus accumbens through the mesolimbic pathway in the ventral tegmental area. Modifying these cells so the team could see when they were stimulated meant they could look for a direct link between a response to gentle touch and Mrgprb4 cells. Indeed, the researchers observed the mice spending more time than usual in the chamber where the light shined, indicating that the mice chose to spend time where a stimulus made them feel good.

Further, Elias and her team modified female mice to disable Mrgprb4 to see how their behavior with males would change. Typically, she says, while there may not be much sexual receptivity during the first meeting, females are more open in following “dates.” However, that wasn’t the case.

“On the second and third trials, it just plummeted instead of increasing,” Elias tells Inverse. “They not only lose the positive reinforcement of sexual receptivity ... and we also see this increasing combative behavior towards the males.” This served as evidence that without Mrgprb4 cells, female mice didn’t get that reward of dopamine when male mice touched them, trying to initiate copulation.

Why it matters — The pandemic showed all of us what happens when we’re deprived of touch, even those quotidian hand brushes and fleeting gestures between friends. To understand the neuroscience behind why touch is so pleasurable is to better understand a part of human well-being. What’s more, it can help us understand conditions that inhibit this feel-good response to gentle touch. A symptom of autism spectrum disorder, for example, is an aversion to light touches; understanding the neuroscience behind why it feels good can help tell us more about how things can go awry.

“In theory, the peripheral nervous system is this untapped therapeutic target,” Elias tells Inverse. Even a topical cream, she says, can easily stimulate the nervous system. She also points to everyday objects that we use to calm the nervous system in the same way that touch can.

“Weighted blankets are a way to mimic a hug, and you get anxiety relief by just activating the peripheral nervous system,” Elias says. “All you're doing is applying pressure around your body, and you see that weighted blankets reduce anxiety.” Even if this study deals more with stroking motions rather than squeezing, “this study is maybe uncovering why that's biologically possible,” according to Elias.

What’s next — Though Elias has moved on to sleep neuroscience at Johns Hopkins University as a postdoctoral researcher, work on this brain circuitry continues.

As far as mice go, they also experience non-sexual touching in many different contexts, even when trying to climb over each other. Females have also been observed to be receptive to touch from each other in a non-sexual way.

“I think that's a big future direction of the lab,” she says.

Still, while mice may offer a clue, we’re still in the dark about how human neurons fire in response to a caress.