A parent’s reassuring touch. A friend’s warm hug. A lover’s enticing embrace. These are among the tactile joys in our lives.
Now,
scientists report previously unidentified starting points in the
neurobiological pathways underlying pleasurable, sexual and otherwise
rewarding social touch. Most notably in their mouse studies, they for
the first time teased out a full pathway that begins with neurons in the
skin that respond to gentle stroking and run all of the way to pleasure
centers of the brain. This research was published in Cell.
The
findings also point toward touch-based therapies for alleviating
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 even tender touch unbearable.
“From
the start, this project had high-risk/high-reward written all over it,”
said the corresponding author on the paper. “We just kept following
the data to where it took us.”
Scientists
have long known the skin features tactile sensory cells–key components
of the peripheral nervous system–that enable us to discern different
textures and temperatures, as well as varieties of pleasurable and
painful mechanical stimuli.
“We
weren’t sure this picture of social touch was quite right,” said the
author. “We set out to test whether there might be tactile neurons
specifically tuned for rewarding touch.”
There
had been hints of this possibility from researchers previously, who
studied a class of sensory cells, dubbed Mrgprb4 cells after a receptor
in their membranes. The scientists found these cells to be responsive to
light strokes.
The new research in Cell is
the culmination of a four-year trajectory of collaborative work
involving nearly 20 scientists from three institutions to look far more
closely at these cells.
Key
to the study was a powerful technique called optogenetics in which
individual cell types are engineered so they can be activated when
researchers shine specific colors of light onto them. The technique is
especially suited for teasing out the functions of specific populations
of cells.
“We
saw that by activating this understudied population of tactile sensory
cells in the mouse’s back that the animals would lower their backs and
take on this posture of dorsiflexion,” said Dr. the lead author. In the
world of rodents, such a posture is a key signature of sexual
receptivity, which normally requires the physical attentions of a suitor
mouse.
“It was very strange. We didn’t know what to make of it,” the author.
At
the heart of this intriguing lead was a line of mice the team
genetically engineered so the animals’s Mrgprb4 touch-sensitive cells
would fire when illuminated with blue light. These types of touch cells
had not previously been linked to any specific social behavior, but when
the authors activated these cells by shining blue light on the mice,
the duo could hardly believe the dorsiflexion responses they were
seeing.
High-speed
video data of the behavior was unmistakable. And later, the research
team observed these same mice voluntarily going to the same spot in the
research chamber where the animals previously had been illuminated. That
was an indication that the animals’ experienced the firing of Mrgprb4
sensory cells in their backs as rewarding.
“This
was the first documented example that a specific behavior might be
generated or supported by these Mrgprb4 neurons,” the senior author
said.
While
the dorsiflexion was fascinating and pointed towards a potential role
for these cells in detecting sexual touch, the researchers needed direct
evidence that they mediated touch during natural social encounters. But
the pandemic intervened and slowed the pace of research. It became so
difficult to move the research forward that by the middle of 2020, the
team considered dropping the project altogether.
At
the 11th hour, however, the authors conducted a crucial experiment.
Using genetic techniques, they eliminated the Mrgprb4 cells. This
enabled the scientists to see if the absence of these cells in touch
circuitry affected the mices’ sexual response to tactile stimulation.
“The
sexual receptivity just plummeted,” the author said. “We then knew for
sure that these cells were important for social touch in natural
encounters.”
Crisp
as this result was, the new data led to a compelling but daunting
research question: how do these peripheral cells link into downstream
neural circuitry through the spinal cord and then more centrally into
the brain?
Answering
this question, the senior author noted, required techniques outside of
the lab’s wheelhouse, which was in the peripheral nervous system. Toward
this end, the author expressed an eagerness for the lab to embrace
fiber photometry, a technique that would allow them to see reward
neurons in the brain “light up” to pleasurable stimuli. Over the next
several months, the authors were able to show that activating Mrgprb4
cells indeed caused neurons to fire in the nucleus accumbens, one of the
brain’s known reward centers.
In
previous studies of touch-involved spinal cord cells, designated as
GPR83 cells, a research group traced neuron-to-neuron links in both
directions: centrally into the brainstem and peripherally to the same
class of Mrgprb4 cells that this team had shown to detect and relay
rewarding touch stimuli.
“That
gave us the handle that these GPR83 neurons are probably a conduit
connecting the skin all of the way to the brain,” said the senior
author.
With
additional experiments–in collaboration, the team managed to track the
skin-to-brain circuitry of touch further and in more detail than had
been achieved previously. One major finding is that the brainstem
neurons the Harvard-led team studied linked to yet deeper locations in
the brain, the ventral tegmental area as well as the nucleus accumbens.
That was a pivotal connection to observe because both brain areas
already were known to be associated with the experience of reward and
pleasure.
The
senior author points out that people have sensory skin cells, called
C-tactile afferents, which have some similarity with the Mrgprb4 cells
in mice. Humans also have spinal cord and brain neurons that correspond
to the touch circuitry that the team and neuroscientists have been
uncovering. These similarities open the way to potential
biomedical applications, the lead said. It could become possible, for
example, to develop peripherally targeted techniques for treating
stress, anxiety or depression–whether through touch therapies or even
novel drugs applied directly to the skin.
“A
cardinal symptom for many people with autism is that they do not like
to be touched,” the senior author added. “This begs the question of
whether the pathway we’ve identified could be altered so people can
benefit from touch that should be rewarding rather than aversive.”
“The
pandemic made us all acutely aware of how devastating the lack of
social and physical contact can be,” the lead said. “I think about the
mental decline of the elderly in nursing homes who could not have
typical contact with visitors. I think about how physical contact
between parents and their newborns and young children is necessary for
proper cognitive and social development. We don’t yet understand how
these kinds of touch convey their benefits, whether acutely pleasurable
or promoting long-term mental wellbeing. That’s why this work is so
essential.”
https://www.cell.com/cell/fulltext/S0092-8674(22)01577-X
http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Ftouch-neurons&filter=22