overview: Research reveals a neural circuit from the skin to the brain that responds to rewarding social touch. The researchers say the findings may provide a means of harnessing the power of physical contact to help treat social and emotional disorders.
sauce: Columbia University
parental reassurance. A warm hug from a friend. The charming embrace of lovers. These are one of the tactile pleasures in our lives.
Now, scientists from the Zuckerman Institute in Columbia and two partner institutions have discovered a previously unidentified initiation of the neurobiological pathways underlying hedonic, sexual, and other rewarding social contact. reporting points. Most notably, a study in mice reveals for the first time a complete pathway that responds to gentle stroking and begins in neurons in the skin leading to the pleasure centers of the brain.
This research is today cell.
The findings also point to contact-based therapies for reducing anxiety, stress and depression, the researchers said. It may even be promising for people with intolerable other conditions.
“From the very beginning, this project had high risk/high reward written all over it,” he said. Ishmael Abdus Sabur PhD, principal investigator and corresponding author of the paper at the Zuckerman Institute, Columbia. “We kept track of where the data took us.”
Scientists have long known the tactile sensory cells (an important component of the peripheral nervous system) that characterize the skin. This allows us to discern different textures and temperatures, as well as different pleasurable and painful mechanical stimuli.
Dr. Abdus-Saboor, who is also an assistant professor of biological sciences at Columbia University, said: “We set out to test whether there are tactile neurons specifically tuned for rewarding touch.”
A Caltech researcher who studied a class of sensory cells gave us a hint of this possibility. This cell he called the Mrgprb4 cell after the receptor in the membrane. Scientists have found that these cells respond to light strokes.
new research in cell is the culmination of four years of collaborative work involving nearly 20 scientists from three institutions (12 from the Abdus-Saboor lab, including the first author) to further explore these cells.
Key to this work was a powerful technique called optogenetics, which allows researchers to manipulate individual cell types so that they can be activated when exposed to specific colors of light. This technique is particularly suitable for eliciting the function of specific cell populations.
The researchers began their study in fall 2018 at the University of Pennsylvania, where Dr. Abdus-Saboor was studying the neuroscience of pain.
Graduate student at that time Leah Elias Then lab technician William Foster (now a graduate student in the Neurobiology and Behavioral Program at Columbia University, cell paper) made a surprising observation.
“By activating this poorly studied population of tactile cells in the mouse’s back, we found that the animals were in a dorsiflexion position with their backs lowered,” said Dr. Elias. In the rodent world, such postures are an important feature of sexual receptivity and typically require physical attention in suitor mice.
“It was very strange,” said Dr. Elias, a postdoctoral fellow at Johns Hopkins University in Baltimore.
At the center of this intriguing lead was a series of mice that the team genetically engineered to make mouse Mrgprb4 touch-sensitive cells fire when illuminated with blue light. These types of contact cells were not previously associated with specific social behaviors, but when Dr. Elias and Foster exposed mice to blue light to activate these cells, the two found that they I could hardly believe the dorsiflexion reaction I saw.
High-speed video data in action was unmistakable.After that, a research team led by a graduate student at the time melanie shuffler, observed these same mice spontaneously going to the same place in the research chamber where the animals had previously been illuminated. This indicated that the animals experienced the firing of Mrgprb4 sensory cells on their backs as a challenge.
“This was the first documented example that a specific behavior may be generated or supported by these Mrgprb4 neurons,” said Dr. Abdus-Saboor.
Although dorsiflexion was intriguing and pointed to a potential role for these cells in detecting sexual contact, researchers found that direct contact mediation during natural social encounters I needed proof.
But the pandemic intervened and slowed the pace of research. The research became so difficult to advance that the team considered abandoning the project altogether by mid-2020.
However, at the eleventh hour, Dr. Elias Isabella SucciA lab technician at the University of Pennsylvania (now a graduate student in the biological sciences program at Columbia University) then performed the important experiments. Using genetic technology, they eliminated her Mrgprb4 cells. This allowed scientists to see if the absence of these cells in the contact circuit affected the sexual response of mice to tactile stimuli.
“Sexual acceptability has plummeted,” Dr. Elias said. “It was then confirmed that these cells were important for social contact in natural encounters.”
Although the results were striking, the new data led to a compelling but difficult research question. How do these peripheral cells link to downstream neural circuits through the spinal cord and centrally to the brain?
In response to this question, Dr. Abdus-Saboor pointed out the need for technology outside the wheelhouse of the lab in the peripheral nervous system. To this end, Dr. Elias has expressed his enthusiasm for the lab to employ his fiber photometry. This is a technique that allows you to see reward neurons in your brain “light up” into pleasurable stimuli.
Over the next few months, Dr. Elias, with significant help from Succi, will show that activating Mrgprb4 cells actually fires neurons in the nucleus accumbens, one of the brain’s known reward centers. I was able to.
But a critical question remained: How did this signal get from the skin to the brain?
As a growing team tackles this multifaceted study in 2020, the Harvard-led study Reported key pieces of a fun touch puzzleThis research group tracked bidirectional interneuronal links in a study of contact-related spinal cord cells, named GPR83 cells. Centrally to the brainstem, peripherally to Dr. Abdus-Saboor’s team and his Mrgprb4 cells in the same class. It was shown to detect and relay rewarding touch stimuli.
“This suggests that these GPR83 neurons are probably conduits that connect the skin to the brain,” said Dr. Abdus-Saboor.
Additional experiments revealed that Victoria Abreira’s Rutgers University LabPh.D. – The team succeeded in tracing the skin-to-brain circuit of contact in more detail than was previously achieved.
One of the major findings is that the brainstem neurons studied by the Harvard-led team are associated with deeper locations in the brain: the ventral tegmental area and the nucleus accumbens. This was a pivotal connection to observe, as both brain regions are already known to be associated with reward and pleasure experiences.
Dr. Abdus-Saboor points out that humans have sensory skin cells called C-tactile afferents, which are similar to mouse Mrgprb4 cells. Humans also have neurons in the spinal cord and brain that correspond to touch circuits that Dr. Abdus Sabour’s team and neuroscientists have uncovered.
These similarities pave the way for potential biomedical applications, Dr. Elias said. For example, it may be possible to develop peripherally targeted techniques to treat stress, anxiety and depression. This is also possible with contact therapy and new drugs applied directly to the skin.
“A basic symptom of many autistic patients is a dislike of being touched,” added Dr. Abdus-Saboor. “This raises the question of whether the pathways we have identified can be altered so that people benefit from rewarding contact rather than aversion.”
“The pandemic has brought home to us just how devastating the lack of social and physical contact can be,” Dr. Elias said.
“I think about the mental decline of elderly people in nursing homes who were unable to have normal contact with their visitors. It is not yet known how this kind of touch can provide benefits. That is why this work is so important.”
Funding: Sources of funding 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. included.
About this sensory neuroscience research news
author: Ivan Amato
sauce: Columbia University
contact: Ivan Amato – Columbia University
image: Image credit goes to Abdus-Saboor Lab/Zuckerman Institute
Original research: open access.
“Touch Neurons Underlying Dopaminergic Pleasure Touch and Sexual Receptivity” by Ishmail Abdus-Saboor et al. cell
Touch neurons underlying dopaminergic hedonic touch and sexual reception
- Activation of Mrgprb4 lineage touch neurons induces a lordosis-like posture
- Activation of Mrgprb4 lineage touch neurons is rewarding
- The Mrgprb4 lineage of touch neurons is required for female sexual acceptance
- The Mrgprb4 lineage of touch neurons engages dopaminergic neurons during social behavior
Pleasant touch is paramount in social behavior, including sexual encounters. However, the identity and precise role of sensory neurons transducing sexual contact remain unclear. A population of sensory neurons labeled by developmental expression of the G protein-coupled receptor Mrgprb4 detects mechanical stimuli in mice.
Here we study the social relevance of Mrgprb4 lineage neurons and reveal that these neurons are necessary for sexual receptivity and sufficient to induce dopamine release in the brain.
Even in social isolation, optogenetic stimulation of Mrgprb4 lineage neurons through the skin of the back induces conditioned place preference and a striking dorsiflexion resembling a lordotic mating posture. enough for
In the absence of the Mrgprb4 lineage of neurons, female mice find male riding less rewarding. Sexual receptivity is replaced by aggression and a concomitant decrease in dopamine release in the nucleus accumbens.
Taken together, these findings establish that neurons of the Mrgprb4 lineage initiate skin-to-brain circuits that encode the rewarding qualities of social contact.