Unraveling the mystery of touch
Researchers have uncovered a mechanism that may explain why certain body
parts are so sensitive

Date:
October 11, 2021
Source:
Harvard Medical School
Summary:
Researchers uncover mechanism that underlies the exquisite
sensitivity of certain skin surfaces. The analysis, conducted in
mice, reveals that the higher sensitivity of certain regions of
the skin stems from a greater number of and stronger connections
between neurons in these regions and corresponding brain areas
that receive signals from them. The findings set the stage for
better understanding the mechanisms that underlie abnormalities
of touch seen in certain neurodevelopmental disorders in humans.



FULL STORY ==========================================================================
Some parts of the body -- our hands and lips, for example -- are more
sensitive than others, making them essential tools in our ability to
discern the most intricate details of the world around us.


==========================================================================
This ability is key to our survival, enabling us to safely navigate our surroundings and quickly understand and respond to new situations. It is perhaps unsurprising that the brain devotes considerable space to these sensitive skin surfaces that are specialized for fine, discriminative
touch and continually gather detailed information via the sensory neurons
that innervate them.

But how does the connection between sensory neurons and the brain result
in such exquisitely sensitive skin? A new study led by researchers at
Harvard Medical School has unveiled a mechanism that may underlie the
greater sensitivity of certain skin regions.

The research, conducted in mice and published Oct. 11 in Cell, shows that
the overrepresentation of sensitive skin surfaces in the brain develops
in early adolescence and can be pinpointed to the brain stem. Moreover,
the sensory neurons that populate the more sensitive parts of the skin
and relay information to the brain stem form more connections and stronger
ones than neurons in less sensitive parts of the body.

"This study provides a mechanistic understanding of why more brain real
estate is devoted to surfaces of the skin with high touch acuity," said
senior author David Ginty, the Edward R. and Anne G. Lefler Professor
of Neurobiology at Harvard Medical School. "Basically, it's a mechanism
that helps explain why one has greater sensory acuity in the parts
of the body that require it." While the study was done in mice, the overrepresentation of sensitive skin regions in the brain is seen across mammals -- suggesting that the mechanism may be generalizable to other
species. From an evolutionary perspective, mammals have dramatically
varied body forms, which translates into sensitivity in different skin surfaces. For example, humans have highly sensitive hands and lips,
while pigs explore the world using highly sensitive snouts. Thus, Ginty
thinks this mechanism could provide the developmental flexibility for
different species to develop sensitivity in different areas.



========================================================================== Moreover, the findings, while fundamental, could someday help illuminate
the touch abnormalities seen in certain neurodevelopmental disorders
in humans.

Scientists have long known that certain body parts are overrepresented
in the brain -- as depicted by the brain's sensory map, called the somatosensory homunculus, a schematic of human body parts and the
corresponding areas in the brain where signals from these body parts
are processed. The striking illustration includes cartoonishly oversized
hands and lips. Previously, it was thought that the overrepresentation
of sensitive skin regions in the brain could be attributed to a higher
density of neurons innervating those skin areas. However, earlier work
by the Ginty lab revealed that while sensitive skin does contain more
neurons, these extra neurons are not sufficient to account for the
additional brain space.

"We noticed that there was a rather meager number of neurons that were innervating the sensitive skin compared to what we'd expect," said
co-first author Brendan Lehnert, a research fellow in neurobiology,
who led the study with Celine Santiago, also a research fellow in the
Ginty lab.

"It just wasn't adding up," Ginty added.

To investigate this contradiction, the researchers conducted a series of experiments in mice that involved imaging the brain and neurons as neurons
were stimulated in different ways. First, they examined how different
skin regions were represented in the brain throughout development. Early
in development, the sensitive, hairless skin on a mouse's paw was
represented in proportion to the density of sensory neurons. However,
between adolescence and adulthood, this sensitive skin became increasingly overrepresented in the brain, even though the density of neurons remained stable -- a shift that was not seen in less sensitive, hairy paw skin.



========================================================================== "This immediately told us that there's something more going on than
just the density of innervation of nerve cells in the skin to account
for this overrepresentation in the brain," Ginty said.

"It was really unexpected to see changes over these postnatal
developmental timepoints," Lehnert added. "This might be just one of
many changes over postnatal development that are important for allowing
us to represent the tactile world around us and helping us gain the
ability to manipulate objects in the world through the sensory motor
loop that touch is such a special part of." Next, the team determined
that the brain stem -- the region at the base of the brain that relays information from sensory neurons to more sophisticated, higher-order
brain regions -- is the location where the enlarged representation of
sensitive skin surfaces occurs. This finding led the researchers to a realization: The overrepresentation of sensitive skin must emerge from
the connections between sensory neurons and brain stem neurons.

To probe even further, the scientists compared the connections between
sensory neurons and brain stem neurons for different types of paw
skin. They found that these connections between neurons were stronger and
more numerous for sensitive, hairless skin than for less sensitive, hairy
skin. Thus, the team concluded, the strength and number of connections
between neurons play a key role in driving overrepresentation of sensitive
skin in the brain. Finally, even when sensory neurons in sensitive skin
weren't stimulated, mice still developed expanded representation in the
brain -- suggesting that skin type, rather than stimulation by touch
over time, causes these brain changes.

"We think we've uncovered a component of this magnification that accounts
for the disproportionate central representation of sensory space." Ginty
said.

"This is a new way of thinking about how this magnification comes about."
Next, the researchers want to investigate how different skin regions
tell the neurons that innervate them to take on different properties,
such as forming more and stronger connections when they innervate
sensitive skin. "What are the signals?" Ginty asked. "That's a big,
big mechanistic question." And while Lehnert describes the study as
purely curiosity-driven, he noted that there is a prevalent class of neurodevelopmental disorders in humans called developmental coordination disorders that affect the connection between touch receptors and the
brain -- and thus might benefit from elucidating further the interplay
between the two.

"This is one of what I hope will be many studies that explore on
a mechanistic level changes in how the body is represented over
development," Lehnert says.

"Celine and I both think this might lead, at some point in the future,
to a better understanding of certain neurodevelopmental disorders." Co-investigators included Erica L. Huey, Alan J. Emanuel, Sophia Renauld, Nusrat Africawala, Ilayda Alkislar, Yang Zheng, Ling Bai, Charalampia Koutsioumpa, Jennifer T. Hong, Alexandra R. Magee,Christopher D. Harvey
of Harvard Medical School.

The research was supported by the National Institutes of Health (F32
NS095631- 01, F32-NS106807, K99 NS119739, DP1 MH125776, R01 NS089521,
and R01 NS97344), a William Randolph Hearst Fellowship, a Goldenson
Fellowship, a Harvard Medical School Dean's Innovation Grant in the
Basic and Social Sciences, and the Edward R. and Anne G. Lefler Center
for the Study of Neurodegenerative Disorders.

========================================================================== Story Source: Materials provided by Harvard_Medical_School. Original
written by Catherine Caruso. Note: Content may be edited for style
and length.


========================================================================== Journal Reference:
1. Brendan P. Lehnert, Celine Santiago, Erica L. Huey, Alan J. Emanuel,
Sophia Renauld, Nusrat Africawala, Ilayda Alkislar, Yang Zheng,
Ling Bai, Charalampia Koutsioumpa, Jennifer T. Hong, Alexandra
R. Magee, Christopher D. Harvey, David D. Ginty. Mechanoreceptor
synapses in the brainstem shape the central representation of
touch. Cell, 2021 DOI: 10.1016/j.cell.2021.09.023 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2021/10/211011110839.htm

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