A Pair of Studies Reveal Surprising New Roles for Both the Spinal Cord and Brain Stem in Communication ScienceDaily

The sense of touch is essential to almost everything we do, from routine tasks around the house to navigating unfamiliar terrain that may hide dangers. Scientists have long been interested in understanding how the touch information we get with our hands and other parts of the body makes its way to the brain to create the sensations we feel.

However, key aspects of touch — including how the spinal cord and brain stem are involved in receiving, processing, and transmitting signals — have remained poorly understood.

Now, a pair of research papers by scientists at Harvard Medical School reveal important new insights into how the spinal cord and brain stem contribute to the sense of touch.

Specifically, the research shows that the spinal cord and brainstem, which were previously thought to be merely relay centers for touch information, are actively involved in the processing of touch signals as they are transmitted to higher-order brain regions.

One study published November 4 in the cellAnd the He shows that specialized nerve cells in the spinal cord form an intricate network that processes light touch — think of a hand brush or a flick on the cheek — and sends that information to the brainstem.

In another study published on November 23 in the natureResearchers have demonstrated that direct and indirect touch pathways work together, converging in the brainstem to shape how touch is processed.

“These studies focus light on the spinal cord and brainstem as sites where touch information is integrated and processed to convey different types of touch. We had not previously fully appreciated how these regions contribute to the brain’s representation of vibration and pressure,” said David Genty, professor of neurobiology at the Blavatnik Institute. at HMS and senior author on both papers, David Ginty, Professor of Neurobiology at the Blavatnik Institute.

Although the studies were done in mice, the mechanisms of touch are largely conserved across species, including humans, which means that the basics of touch processing could be useful to scientists studying human conditions such as neuropathic pain characterized by touch impairment.

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

Ignoring and underestimating it

The historical view of touch is that sensory neurons in the skin experience tactile stimuli such as pressure or vibration and send this information in the form of electrical impulses that travel directly from the skin to the brainstem. There, other neurons relay touch information to the brain’s primary somatosensory cortex—the highest level in the tactile hierarchy—where it is processed into sensation.

However, Genty and his team wondered if and how the spinal cord and brainstem are involved in processing touch information. These regions occupy the lowest level of the touch hierarchy, and combine to form an indirect communication pathway to the brain.

said Josef Turicek, a postdoctoral fellow in Genty’s lab and first author on nature paper.

Turecek explained that many neuroscientists aren’t familiar with neurons in the spinal cord, called postsynaptic neurons (PSDCs), that project from the spinal cord to the brainstem — and textbooks tend to leave PSDC neurons out of the graphs that depict touch details. .

For Genty, the way the spinal cord and brainstem were overlooked by touch is reminiscent of early research on the visual system. At first, scientists who study vision believed that all processing took place in the visual cortex of the brain. However, the retina, which receives visual information long before it reaches the cerebral cortex, has been shown to be highly involved in processing this information.

“Similar to research in the visual system, these two papers look at how tactile information coming from the skin is processed in the spinal cord and brainstem before it travels down the tactile hierarchy to more complex brain regions,” Genty said.

Connect the dots

In the cell On paper, the researchers used a technique they developed to record the activity of many different neurons in the spinal cord simultaneously as the mice experienced different types of touch. They discovered that more than 90 percent of neurons in the dorsal horn — the sensory processing area of ​​the spinal cord — responded to light touch.

“This was surprising because dorsal horn neurons in the superficial layers of the spinal cord were traditionally thought to respond mostly to temperature and painful stimuli. We had not appreciated how light touch information is distributed in the spinal cord,” Anda Schirella said. , a research fellow in Genty’s lab and co-lead author on the paper with graduate student Jenelle Rankin.

Moreover, these responses to light touch varied significantly across genetically different groups of neurons in the dorsal horn, which were found to form a highly interconnected and complex neural network. This difference in responses in turn gave rise to a variety of touch information transmitted from the dorsal horn to the brainstem by PSDC neurons. Indeed, when the researchers silenced many dorsal horn neurons, they observed a decrease in the diversity of light touch information transmitted by PSDC neurons.

“We believe that this information about how touch is encoded in the spinal cord, which is the first location in the touch hierarchy, is important for understanding fundamental aspects of touch processing,” Sherella said.

In their other study published in nature, the scientists focused on the next step in the touch hierarchy: the brainstem. They explored the relationship between the direct pathway from sensory neurons in the skin to the brainstem and the indirect pathway that sends tactile information through the spinal cord, as shown in cell paper.

“Neural cells in the brainstem get 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 alternately silenced each pathway and recorded the response of neurons in the mouse brainstems. Experiments have shown that the direct path is important for the conduction of high-frequency vibrations, while the indirect path 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 those neurons’ responses based on how much direct and indirect input you have,” Turecek explained. In other words, if neurons in the brainstem have more direct input than indirect input, they transmit a vibration of more intensity, and vice versa.

In addition, the team discovered that both pathways can transmit touch information from the same small area of ​​skin, with information about the intensity of convolutions through the spinal cord before combining information about vibrations transmitted directly to the brainstem. In this way, the direct and indirect pathways work together, enabling the brainstem to form a spatial representation of different types of touch stimuli from the same region.

Finally on the map

Until now, “most people considered the brainstem as a relay station for touch, and they didn’t even have the spinal cord on the map at all,” Genty said. For him, the new studies “show that an enormous amount of information processing takes place in the spinal cord and brainstem—and that processing is essential to how the brain represents the world of touch.”

He added that such processing likely contributes to the complexity and diversity of touch information that the brainstem sends to the somatosensory cortex.

Next, Genty and his team plan to repeat the experiments on mice that were awake and behaving, to test the results under more natural conditions. They also want to extend experiences to more types of real-world touch stimuli, such as texture and motion.

Researchers are also interested in how information from the brain—for example, about an animal’s level of stress, hunger, or fatigue—affects how touch information is processed in the spinal cord and brainstem. Given that the mechanisms of touch appear to be conserved across species, this information may be particularly relevant for human conditions such as autism spectrum disorders or neuropathic pain, where neuronal dysfunction causes hypersensitivity to light touch.

“With these studies we have laid out the building blocks of how these circuits work and what they are important,” Rankin said. “Now we have the tools to dissect these circuits to understand how they function normally, and what changes when something goes wrong.”

Authoring and financing

Additional authors on cell The paper includes Shih Yi Zeng, Alan Emanuel, Carmine Chavez Martinez, Dawei Zhang, and Christopher Harvey of HMS. Additional authors on nature The paper includes Brendan Lehnert of HMS.

support for cell The paper was submitted by the Harvard Mahoney Neuroscience Institute, Ellen R. and Melvin Gordon Center for Paralysis and Treatment, National Science Foundation (GRFP DG1745303), Stewart HQ and Victoria Cowan Fellowship, National Institutes of Health (MH125776; NS089521; NS119739; NS097344; AT011447), and the Center Hawk E. Tan and K.K. Lisa Yang Research Center for Autism, and the Edward R and Ann G. Leffler Center for the Study of Neurodegenerative Disorders.

support for nature The paper was provided by the Harvard Mahoney Neuroscience Institute, and the Ellen R and Melvin J. Gordon Paralysis Clinic and Treatment, National Institutes of Health (NS097344; AT011447), Hawk E. Tan and K.K. for Autism Research, and the Edward R and Ann G. Leffler Center for the Study of Neurodegenerative Disorders.

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