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Touch: Mysteries Unravel why some skin patches are sensitive

Some areas of the body, such as our hands and lips, are more sensitive than others, making them crucial instruments in our ability to identify the most minute details of our surroundings.

This capacity is critical to our survival because it allows us to navigate our surroundings securely and swiftly comprehend and respond to novel events. It's perhaps not surprising that the brain gives these sensitive skin surfaces, which are specialized for fine, discriminative touch and constantly acquire precise information via the sensory neurons that innervate them, a lot of attention.

But how does the brain's link with sensory neurons lead to such extraordinarily sensitive skin?

A new study led by Harvard Medical School researchers has discovered a mechanism that could explain why certain skin patches are more sensitive than others.

The study, which was conducted in mice and published in Cell on Oct. 11, found that the brain's overrepresentation of sensitive skin surfaces emerges in early adolescence and can be traced back to the brain stem. Furthermore, sensory neurons in more sensitive areas of the skin that transmit information to the brain stem make more and stronger connections than neurons in less sensitive areas of the body.

Senior author David Ginty, the Edward R. and Anne G. Lefler Professor of Neurobiology at Harvard Medical School, said, "This study provides a mechanistic understanding of why more brain real estate is devoted to skin surfaces with high touch acuity." "Essentially, it's a system that explains why certain regions of the body demand more sensory acuity."

The overrepresentation of sensitive skin regions in the brain is evident throughout mammals, suggesting that the method could be generalized to other species.

Mammals have a wide range of body shapes, which translates to differing levels of sensitivity on different skin surfaces. Humans, for example, have extremely sensitive hands and lips, whereas pigs have extremely sensitive snouts. Ginty believes that this technique could allow various species to gain sensitivity in different regions as a result of their developmental flexibility.

Furthermore, while the findings are fundamental, they may one day assist to explain the abnormalities in touch reported in certain neurodevelopmental diseases in humans.

The somatosensory homunculus, a schematic of human body parts and the associated areas in the brain where signals from these body parts are processed, has long been known to scientists that certain body parts are overrepresented in the brain. The striking illustration features oversized hands and lips that are cartoonishly oversized. The overrepresentation of sensitive skin regions in the brain was previously assumed to be due to a larger density of neurons innervating certain skin areas.

However, previous research from the Ginty group found that while sensitive skin has more neurons, these extra neurons are insufficient to account for the increased brain space.

"We discovered that there were a relatively small amount of neurons innervating the sensitive skin compared to what we'd expect," said Brendan Lehnert, a neurobiology research fellow who co-led the study with Celine Santiago, another Ginty lab research member.

"It just didn't add up," Ginty continued.

To study this discrepancy, the researchers used mice to conduct a series of tests that included imaging the brain and neurons as they were stimulated in various ways. They started by looking at how different skin regions were represented in the brain as they developed. The sensitive, hairless skin on a mouse's paw was depicted in proportion to the density of sensory neurons early in development. However, this sensitive skin became more overrepresented in the brain during adolescence and maturity, even while the density of neurons remained consistent — a shift that was not found in less sensitive, hairy paw skin.

"This immediately alerted us that there's more going on than just the density of nerve cell innervation in the epidermis to explain this overrepresentation in the brain," Ginty explained.

"Seeing differences during these postnatal developmental timepoints was absolutely unexpected," Lehnert remarked. "This could be just one of many changes that occur during postnatal development that are critical for allowing us to represent the tactile world around us and for allowing us to handle objects in the world through the sensory motor loop, which touch is such a key aspect of."

The team next discovered that the larger representation of sensitive skin surfaces occurs in the brain stem, an area at the base of the brain that transfers information from sensory neurons to more sophisticated, higher-order brain regions. The researchers came to the following conclusion as a result of their discovery:

The connections between sensory neurons and brain stem neurons must be the source of the overrepresentation of sensitive skin.

The researchers studied the connections between sensory neurons and brain stem neurons in different types of paw skin to dig further. They discovered that for sensitive, hairless skin, these connections between neurons were stronger and more numerous than for less sensitive, hairy skin. The intensity and quantity of connections between neurons, the researchers concluded, play a significant role in generating overrepresentation of sensitive skin in the brain. Finally, mice gained increased representation in the brain even when sensory neurons in sensitive skin were not activated, implying that skin type, rather than activation by touch over time, drives these brain alterations.

"We believe we've discovered a component of this magnification that explains the exaggerated central representation of sensory space," says the researcher. Ginty remarked. "This is a different way of looking at how magnification works."

The researchers now aim to look into how different skin regions instruct their innervating neurons to take on distinct characteristics, such as forming more and stronger connections when innervating sensitive skin. Ginty inquired, "What are the signals?" "That's a huge mechanistic problem."

While Lehnert describes the research as purely exploratory, he points out that there is a common class of neurodevelopmental disorders in humans known as developmental coordination disorders that affect the connection between touch receptors and the brain, and thus elucidating the interaction between the two could be beneficial.

"This is the first of what I hope will be many studies that look at changes in how the body is represented throughout time on a mechanical level," Lehnert adds. "Celine and I both believe that this will lead to a better understanding of certain neurodevelopmental problems in the future."

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