Researchers discover the origin of pleasant touch in the brain

Researchers report previously unknown starting points in the neurobiological pathways underlying pleasurable, sexual, and otherwise beneficial social touch. (CREDIT: Kayla Da Silva/McMaster University)

The reassuring touch of a parent. Warm hugs from a friend. The seductive embrace of a lover. It is one of the tactile joys in our lives.

Now scientists at Columbia’s Zuckerman Institute and two partner institutions are reporting previously unknown entry points in the neurobiological pathways that underlie pleasurable, sexual and other rewarding social encounters. In particular, in their studies on mice, they are the first to identify a complete pathway that starts with neurons in the skin that respond to light strokes and goes all the way to pleasure centers in the brain. This study was published in Cell.

The findings also point to a touch-based therapy for relieving anxiety, stress and depression, the researchers said. What’s more, such therapy could be promising for people with autism and other conditions that can make even gentle touch unbearable.

“From the beginning, this project was written high risk/high reward,” said Ishmail Abdus-Sabur, Ph.D., principal investigator at the Columbia Zuckerman Institute and corresponding author of the paper. “We just kept following the data where it took us.”

Similar stories

Scientists have long known that the skin contains tactile sensory cells—key components of the peripheral nervous system—that allow us to distinguish between different textures and temperatures, as well as various pleasant and painful mechanical stimuli.

“We weren’t sure that this picture of social contact was entirely correct,” said Dr. Abdus-Sabur, who is also an assistant professor of biological sciences at Columbia University. “We set out to test whether there could be tactile neurons specifically tuned for rewarding touch.”

This possibility was hinted at by Caltech researchers studying a class of sensory cells named Mrgprb4 cells after a receptor in their membranes. Scientists have found that these cells respond to light shocks.

Neurons that project into the ventral tegmental region (in blue)—a region of the brain associated with pleasure and reward—receive projections from spinal cord neurons (in red), which themselves receive sensory input, detecting direct skin interaction. with body. brain circuit for pleasurable touch in mice. (TEACHER: Abdus-Sabur Laboratory/Zuckerman Institute)

New research in Cell is the culmination of a four-year collaborative effort involving almost 20 scientists (12 from the Abdus-Sabur lab, including the first author) from three institutions to study these cells more closely.

Key to the study was a powerful technique called optogenetics, in which individual cell types are engineered to be activated when researchers illuminate them with specific colors of light. This method is particularly suitable for identifying the functions of certain cell populations.

The researchers began their research in the fall of 2018 at the University of Pennsylvania, when Dr. Abdus-Sabour was a professor there studying the neurology of pain. It was then that graduate student Leah Elias, and then laboratory assistant William Foster (now a graduate student at Columbia University in the Neuroscience and Behavior Program and the first author Cell paper) made a startling observation.

Fluorescent green features in this photomicrograph of hairy skin on the back of a mouse indicate the presence of tactile sensory cells in the Mrgprb4 cell line. (TEACHER: Abdus-Sabur Laboratory/Zuckerman Institute)

“We saw that when this little-studied population of tactile sensory cells was activated on the back of a mouse, the animals lowered their back and assumed this dorsiflexion posture,” Dr. Elias said. In the rodent world, this posture is a key sign of sexual receptivity, which usually requires the physical attention of a suitor mouse.

“It was very strange. We didn’t know what to do with it,” said Dr. Elias, now a postdoctoral fellow at Johns Hopkins University in Baltimore.

At the heart of this intriguing clue was a line of mice that the team had genetically engineered to make their Mrgprb4 sensory cells fire when illuminated with blue light. These types of sensory cells had not previously been associated with any specific social behavior, but when Dr. Elias and Foster activated these cells by exposing mice to blue light, the duo could hardly believe the dorsiflexion response they were seeing.

The neurons of the Mrgprb4 lineage are essential for female sexual receptivity. (CREDIT: Cellular)

The high-speed video data on behavior was unmistakable. And later, a research team led by then graduate student Melanie Schaffler observed these same mice voluntarily walk to the same spot in the research chamber where the animals had previously been lit. This indicated that the activation of Mrgprb4 sensory cells in the back of the animals was perceived as a reward.

“This was the first documented example that a particular behavior can be generated or maintained by these Mrgprb4 neurons,” Dr. Abdus-Sabur said.

Although dorsiflexion was exciting and indicated a potential role for these cells in detecting sexual touch, the researchers needed direct evidence that they mediate touch during natural social encounters. But the pandemic intervened and slowed down the pace of research. It became so difficult to advance research that by mid-2020, the team decided to abandon the project altogether.

However, at 11 o’clock, Dr. Elias, who was working with Isabella Succi, then a laboratory assistant at the University of Pennsylvania laboratory (now a graduate student at Columbia University in the biological sciences program), performed a decisive experiment. Using genetic methods, they removed the Mrgprb4 cells. This allowed the scientists to see if the absence of these cells in the tactile circuit affected the mice’s sexual response to tactile stimulation.

“Sexual receptivity plummeted,” said Dr. Elias. “Then we knew for sure that these cells are important for social contact in natural contacts.”

As clear-cut as this result is, the new data has led to a compelling but frightening research question: How do these peripheral cells connect to downstream neural circuits via the spinal cord and then more centrally to the brain?

In response to this question, Dr. Abdus-Sabour noted that methods are required outside the wheelhouse of the laboratory, which is located in the peripheral nervous system. To that end, Dr. Elias expressed his wish that the lab implement fiber photometry, a technique that would allow them to see how reward neurons in the brain “fire” in response to pleasant stimuli. Over the next few months, with decisive help from Succi, Dr. Elias was able to show that activating Mrgprb4 cells did in fact fire neurons in the nucleus accumbens, one of the brain’s known reward centers.

But the critical question remained: how did this signal get from the skin to the brain?

When a growing team took on this multi-faceted study in 2020, the Harvard-led study reported the telling part of the pleasant touch puzzle. In their study of spinal cord cells involved in touch, designated GPR83 cells, this research team traced connections between neurons in both directions: centrally to the brainstem and peripherally to the same Mrgprb4 cell class as Dr. Abdus-Sabour’s group. have shown to detect and transmit rewarding sensory stimuli.

“This gave us the idea that these GPR83 neurons are probably the conduit that connects the skin all the way to the brain,” said Dr. Abdus-Sabour.

With additional experiments — in collaboration with the Rutgers University lab of Victoria Abraira, Ph.D. — the team was able to trace the skin-to-brain touch pattern further and in more detail than previously achieved. One important finding is that the brainstem neurons that the Harvard team studied are connected to even deeper regions of the brain, the ventral tegmental region, as well as the nucleus accumbens. This was a key link to observe, since both areas of the brain were already known to be associated with the experience of reward and pleasure.

Dr. Abdus-Sabour notes that humans have sensory skin cells called C-tactile afferents that bear some resemblance to Mrgprb4 cells in mice. Humans also have neurons in the spinal cord and brain that match the touch patterns discovered by Dr. Abdus-Sabur’s team and neuroscientists. These similarities pave the way for potential biomedical applications, Dr. Elias says. For example, it will be possible to develop peripherally targeted treatments for stress, anxiety, or depression—whether through tactile therapy or even new drugs applied directly to the skin.

“The main symptom of many people with autism is that they don’t like being touched,” added Dr. Abdus-Sabour. “This raises the question of whether the pathway we have identified can be modified so that people can benefit from touch that should be helpful rather than repulsive.”

“The pandemic has made us all acutely aware of how devastating a lack of social and physical contact can be,” said Dr. Elias. “I think about the mental decline of older people in nursing homes who were unable to interact properly with visitors. I think that physical contact between parents and their newborns and young children is essential for proper cognitive and social development. We don’t yet understand how these types of touch convey their benefits, whether they provide spicy pleasure or promote long-term mental well-being. That’s why this work is so important.”

For more science news, visit our New Discoveries section at The bright side of the news.

Note: Materials provided above by Columbia University. Content can be edited for style and length.

Do you like such pleasant stories? Receive Brighter Side of News Newsletter.