Trace the origins of pleasurable touch from the skin to the brain

summary: The study reveals a neural circuit from the skin to the brain that responds to rewarding forms of social touch. The researchers say the findings could provide a way to harness the power of touch to help treat social and emotional disorders.

Source: Columbia University

A parent’s reassuring touch. A warm friend hug. cuddly hug This is among the joys of touch in our lives.

Now, scientists at the Zuckerman Institute in Columbia and two partner institutions have reported previously unidentified trigger points in the neurobiological pathways underlying pleasurable, sexual, and rewarding social touch. Most notably in their mouse studies, they have for the first time brought out an entire pathway that begins with neurons in the skin that respond to gentle strokes and travels to the pleasure centers of the brain.

This research was published today in cell.

The findings also point to touch-based therapies for relieving anxiety, stress and depression, the researchers said. What’s more, such therapies may hold promise for those with autism and other conditions that can make gentle touch unbearable.

“From the very beginning, this high risk/reward project was written all over it,” he said Ishmail Abdus-Saboor, PhD, principal investigator at the Zuckerman Institute at Columbia and corresponding author on the paper. “We have continued to follow the data to where it has taken us.”

Scientists have long known that the skin features tactile sensory cells—key components of the peripheral nervous system—that enable us to distinguish different textures and temperatures, as well as different types of mechanical stimuli that are both pleasant and painful.

“We weren’t sure that this picture of social touch was quite right,” said Dr. Abdel-Sabour, also an assistant professor of biological sciences at Columbia University. “We set out to test whether there were tactile neurons that were specifically tuned to the reward of touch.”

There have been hints of this possibility from researchers at Caltech, who studied a class of sensory cells, dubbed Mrgprb4 cells after a receptor in their membranes. Scientists have found that these cells respond to light strokes.

New search in cell It is the culmination of a four-year course of collaborative work that involved nearly 20 scientists (12 from Abdel-Sabour’s lab, including the first author) from three institutions to look closely at these cells.

Key to the study was a powerful technique called optogenetics in which individual cell types are engineered so that they can be activated when researchers shine certain colors of light on them. This technique is particularly suitable for extracting functions of specific groups of cells.

The researchers began their exploration in the fall of 2018 at the University of Pennsylvania, when Dr. Abdel-Sabour was a faculty member there studying the neuroscience of pain.

That’s when you graduate after that student Leah Elias Then lab technician William Foster (now a graduate student at Columbia University in the Neuroscience and Behavioral Program and first author on cell paper) made a startling remark.

“We saw that by activating this little-studied group of tactile sensory cells in the mouse’s back, the animals would lower their backs and assume this dorsiflexion position,” said Dr. Elias. In the rodent world, such a situation is a major sign of sexual acceptance, which usually requires the physical attention of a suitor rat.

“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 lead was a group of mice that the team had genetically engineered so that Mrgprb4’s touch-sensitive cells would fire when illuminated with blue light. These types of tactile cells had not previously been linked to any specific social behavior, but when Dr. Elias and Foster activated these cells by shining blue light on the mice, the duo couldn’t believe the back sympathy responses they saw.

The high-speed video data for the behavior was unequivocal. Next, the research team is led by a graduate student Melanie SchefflerObserve these same mice voluntarily go to the same spot in the research room where the animals were previously lit. This was an indication that the animals experienced Mrgprb4 sensory cell firing at their appearance as a reward.

“This was the first documented example that a specific behavior might be generated or supported by Mrgprb4 neurons,” said Dr. Abdel-Sabour.

While the dorsiflexion was remarkable and indicated a possible role for these cells in detecting sexual touch, the researchers needed direct evidence that they mediate touch during normal social encounters.

But the pandemic intervened and slowed the pace of research. It became so difficult to move forward with the research that by mid-2020 the team considered dropping the project altogether.

At the eleventh hour, Dr. Elias works with Isabella Sochi, then a lab technician at Penn (now a graduate student in Columbia University’s biological sciences program), conducted a crucial experiment. Using genetic techniques, Mrgprb4 cells were knocked out. This enabled the scientists to see if the absence of these cells in the touch circuits affected the rats’ sexual response to tactile stimulation.

“Sexual receptivity just went down,” said Dr. Elias. “Then we definitely knew that these cells are important for social influence in natural encounters.”

As obvious as this finding was, the new data prompted a compelling but daunting research question: How do these peripheral cells connect to neural circuits downstream through the spinal cord and then more centrally in the brain?

In response to this question, Dr. Abdel-Sabour indicated that the required techniques are outside the laboratory command room, which was located in the peripheral nervous system. To that end, Dr. Elias is eager for the lab to embrace fibrephotometry, a technique that allows them to see equivalent neurons in the brain “light up” to pleasurable stimuli.

Over the next few months, with crucial help from Succi, Dr. Elias was able to show that activation of Mrgprb4 cells did indeed cause neurons to fire in the nucleus accumbens, one of the brain’s well-known reward centers.

But an important question remains: How does this signal get from the skin to the brain?

As the growing team took on this multifaceted research in 2020, a Harvard-led study I reported a telling piece of the fun tactile puzzle. In their studies of spinal cord touch cells, known as GPR83 cells, this research group traced the synaptic connections between neurons in both directions: centrally in the brainstem and peripherally to the same class of Mrgprb4 cells that Dr. Abdel-Sabour’s team did. has demonstrated the detection and relay of rewarding tactile stimuli.

“This gave us the understanding that these GPR83 neurons are probably a channel that connects the skin all the way to the brain,” said Dr. Abdel-Sabour.

With additional experiences – in collaboration with Rutgers University Laboratory in Victoria AbreraPh.D. — the team was able to track the touch circuits from the skin to the brain in greater scale and with more detail than had been achieved previously.

This shows neurons in the vta
Neurons projecting to the ventral tegmental area (in blue)—a brain region associated with pleasure and reward—in turn receive projections from neurons in the spinal cord (in red) which themselves receive tactile inputs, revealing a direct orientation to the skin. Brain circuit for a pleasant touch in mice. Credit: Abdel-Sabour Lab/Zuckerman Institute

One key finding is that neurons in the brainstem that the Harvard-led team studied are connected to deeper sites in the brain, the ventral tectorial region as well as the nucleus accumbens. This was a pivotal connection to monitor because both regions of the brain were already known to be associated with the experience of reward and pleasure.

And Dr. Abdel-Sabour notes that humans have sensory skin cells, called the touch afferent C, that have some similarities to Mrgprb4 cells in mice. Humans also have spinal cord and brain neurons that correspond to touch circuits discovered by Dr. Abdel-Sabour’s team and neuroscientists.

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Dr. Elias said these similarities open the way for potential biomedical applications. It may become possible, for example, to develop peripherally targeted technologies for treating stress, anxiety, or depression — whether through touch therapies or even new medications applied directly to the skin.

Dr. Abdel-Sabour added, “One of the main symptoms for many people with autism is that they do not like being touched.” “This begs the question whether the pathway we’ve set out can be altered so that people can benefit from touch, which should be rewarding rather than aversive.”

“The pandemic has made us all acutely aware of how devastating the lack of social and physical contact can be,” said Dr. Elias.

“I think of the mental deterioration of elderly people in nursing homes who were unable to have usual contact with visitors. I think of how important physical contact between parents and newborns and young children is for proper cognitive and social development. We don’t yet understand how these types of touch convey their benefits, either. It was very pleasurable or promote mental well-being in the long term. That is why this work is so necessary.”

Funding: Funding sources and support include the University of Pennsylvania, Columbia University, Rutgers University, the National Institutes of Health (including NINDS), the Rita Allen Foundation, the Pew Charitable Trust, the Brain Research Foundation, the Alfred P. Sloan Foundation, and the Whitehall Foundation.

About this research news Sensory Neuroscience

author: Evan Amato
Source: Columbia University
Contact: Ivan Amato – Columbia University
picture: Image credit: Abdel Sabour Lab/Zuckerman Institute

Original search: open access.
Touch neurons underlying pleasurable dopamine touch and sexual kissingIsmail Abdel-Sabour and others. cell


Summary

Touch neurons underlying pleasurable dopamine touch and sexual kissing

Highlights

  • Activation of Mrgprb4-lineage touch neurons induces a lordosis-like position
  • Activation of Mrgprb4-lineage touch neurons is rewarding
  • Mrgprb4 touch neurons are required for female sexual receptivity
  • Mrgprb4-lineage touch neurons engage dopaminergic neurons during social behaviour

summary

Pleasant touch is crucial during social behavior, including sexual encounters. However, the exact identity and role of sensory neurons that transmit sexual touch remains unknown. A population of sensory neurons labeled with developmental expression of the G protein-coupled receptor Mrgprb4 detects mechanical stimulation in mice.

Here, we examine the social significance of Mrgprb4-lineage neurons and reveal that these neurons are required for sexual receptivity and sufficient to induce dopamine release in the brain.

Even in social isolation, optogenetic stimulation of Mrgprb4 neurons through the posterior epidermis is sufficient to induce conditioned place preference and striking dorsal flexion resembling the lordous copulation position.

In the absence of Mrgprb4 neurons, female mice no longer find rewarding male mounts: sexual receptivity is replaced by aggressiveness and a corresponding decrease in dopamine release in the nucleus accumbens.

Together, these results demonstrate that Mrgprb4 neurons initiate a skin-to-brain circuit encoding the rewarding quality of social touch.

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