Two research reveal shocking new roles for spinal cord-brain stem contact

The sense of touch is essential to almost everything we do, from routine household chores to navigating unfamiliar terrain that can be dangerous. Scientists have long been interested in understanding exactly how the tactile information we receive from our hands and other body parts travels to the brain to create the sensations we feel.

Still, key aspects of touch—including how the spinal cord and brainstem are involved in receiving, processing, and transmitting signals—are still poorly understood.

Now, two publications by Harvard Medical School scientists reveal important new insights into how the spinal cord and brainstem contribute to the sense of touch.

In particular, research shows that the spinal cord and brainstem, previously thought to be merely relay centers for tactile information, are actively involved in processing tactile signals as they travel to higher-order brain regions.

A study published Nov. 4 in cell, shows that specialized neurons in the spinal cord form a complex network that processes light touch—think a touch of a hand or a kiss on the cheek—and sends that information to the brainstem.

In another study, published Nov. 23 in NatureResearchers have found that direct and indirect pathways of touch work together and converge in the brainstem to affect touch processing.

“These studies focus on the spinal cord and brainstem as sites where tactile information is integrated and processed to mediate different types of touch. We had not yet fully understood how these areas contribute to the representation of vibration, pressure and other features of tactile stimuli in the brain,” said David Ginty, Edward R. and Anne G. Lefler, Professor of Neurobiology at HMS Blavatnik Institute and lead author both papers.

Although the studies were conducted in mice, touch mechanisms are largely conserved in all species, including humans, meaning the basics of tactile processing could be useful to scientists studying human disorders such as neuropathic pain, which are characterized by touch disorders.

“This detailed understanding of tactile sensation — that is, sensing the world through skin contact — can have profound implications for understanding how disease, disorders and injury can affect our ability to interact with the environment around us,” said James. Gnadt, program director at the National Institute of Neurological Disorders and Stroke (NINDS), who provided some funding for the studies.

Overlooked and underestimated

The historical view of touch is that sensory neurons in the skin encounter a tactile stimulus, such as pressure or vibration, and send that information in the form of electrical impulses that travel directly from the skin to the brainstem. There, other neurons transmit tactile information to the brain’s primary somatosensory cortex — the highest level of the tactile hierarchy — where it is converted into sensations.

However, Ginty and his team wondered if and how the spinal cord and brainstem are involved in processing tactile information. These areas occupy the lowest level of the tactile hierarchy and together form a more indirect tactile pathway in the brain.

“People in this field used to think that the variety and richness of touch came only from sensory neurons in the skin, but thinking bypasses the spinal cord and brainstem,” said Josef Turecek, a postdoctoral fellow at the Ginty Lab and first author of Nature Paper.

Many neuroscientists are unfamiliar with spinal cord neurons called postsynaptic dorsal column neurons (PSDCs), which project from the spinal cord into the brainstem — and textbooks tend to leave PSDC neurons aside from diagrams describing touch details, Turecek explained.

For Ginty, the way the spinal cord and brainstem were neglected in touch is reminiscent of early exploration of the visual system. Initially, scientists studying vision thought that all processing took place in the brain’s visual cortex. However, it turns out that the retina, which receives visual information long before it reaches the cortex, is heavily involved in processing that information.

“Similar to research into the visual system, these two papers address how tactile information is processed from the skin in the spinal cord and brainstem before ascending the tactile hierarchy to more complex brain regions,” Ginty said.

Connect the dots

In which cell In the article, the researchers used a technique they developed to simultaneously record the activity of many different neurons in the spinal cord when mice experienced different types of touch. They found that over 90% of neurons in the dorsal horn – the sensory processing area of ​​the spinal cord – responded to light touch.

“This was surprising because it was traditionally thought that the dorsal horn neurons in the superficial layers of the spinal cord responded primarily to temperature and pain stimuli. We didn’t know how light tactile information is distributed in the spinal cord,” said Anda Chirila. , researcher at Ginty Lab and co-first author of the article with graduate student Genelle Rankin.

Furthermore, these responses to light touch varied greatly between genetically distinct populations of dorsal horn neurons, forming a highly interconnected and complex neural network. These different responses, in turn, led to a variety of tactile information being carried by PSDC neurons from the dorsal horn to the brainstem. Indeed, when the researchers silenced various dorsal horn neurons, they found a reduction in the variety of light tactile information transmitted by PSDC neurons.

“We believe this information about how touch is encoded in the spinal cord, the first site of the tactile hierarchy, is important for understanding fundamental aspects of tactile processing,” Chirila said.

In their other study, published in Naturethe scientists focused on the next level in the tactile hierarchy: the brainstem. They examined the relationship between the direct pathway of sensory neurons from the skin to the brainstem and the indirect pathway that sends tactile information through the spinal cord, as described in cell Paper.

“Brainstem neurons receive direct and indirect inputs, and we were really curious about what aspects of touch each pathway brings to the brainstem,” Turecek said.

To analyze this question, the researchers turned off each signaling pathway and recorded the response of neurons in the brainstem of mice. Experiments have shown that the direct route is important for the transmission of high-frequency vibrations, while the indirect route is necessary for encoding the intensity of pressure on the skin.

“The idea is that these two pathways converge in the brainstem with neurons that can encode both vibration and intensity, so you can shape the responses of those neurons based on the amount of direct and indirect input,” explained Turecek. In other words, when brainstem neurons have more direct than indirect inputs, they communicate more vibration than intensity, and vice versa.

In addition, the team found that both pathways can transmit tactile information from the same small area of ​​skin, with intensity information diverging through the spinal cord before combining with vibrational information that follows and traveling directly to the brainstem. In this way, the direct and indirect pathways work together, allowing the brainstem to form a spatial representation of different types of tactile stimuli coming from the same area.

Finally on the map

Until now, “most people thought of the brainstem as a relay station for touch, and they didn’t have the spinal cord on the map at all,” Ginty said. For him, “the new studies show that there is a tremendous amount of information processing going on in the spinal cord and brainstem — and this processing is essential to how the brain represents the tactile world.”

Such processing, he added, likely contributes to the complexity and variety of tactile information that the brainstem sends to the somatosensory cortex.

Next, Ginty and his team plan to replicate the experiments in awake, behaving mice to test the results in more natural conditions. They also want to expand the experiments to include more types of real tactile stimuli, such as texture and movement.

The researchers are also interested in how information from the brain – for example about stress, hunger or exhaustion in an animal – affects the processing of tactile information in the spinal cord and brainstem. Because the mechanisms of touch appear to be conserved across species, this information may be particularly relevant to human conditions such as autism spectrum disorders or neuropathic pain, in which neuronal dysfunction causes hypersensitivity to light touch.

“Through these studies, we have laid the fundamental foundation for how these circuits work and why they are important,” Rankin said. “We now have the tools to analyze these circuits to understand how they normally work and what changes when something goes wrong. »

Authorship and Funding

Other authors on the cell Items include Shih-Yi Tseng, Alan Emanuel, Carmine Chavez-Martinez, Dawei Zhang and Christopher Harvey from HMS. Other authors on the Nature Items belong to Brendan Lehnert of HMS.

support for cell The article was supported by the Harvard Mahoney Neuroscience Institute, the Ellen R. and Melvin J. Gordon Center for the Cure and Treatment of Paralysis, the National Science Foundation (GRFP DG1745303), a Stuart HQ & Victoria Quan Fellowship, the National Institutes of Health ( MH125776; NS089521; NS119739; NS097344; AT011447), the Hock E. Tan and K. Lisa Yang Center for Autism Research, and the Edward R. and Anne G. Lefler Center for the Study of Neurodegenerative Disorders.

support for Nature Article courtesy of Harvard Mahoney Neuroscience Institute, Ellen R. and Melvin J. Gordon Center for the Cure and Treatment of Paralysis, National Institutes of Health (NS097344; AT011447), Hock E. Tan, and K. Lisa Yang Center for Autism Research and the Edward R. and Anne G. Lefler Center for the Study of Neurodegenerative Disorders.

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