Almost all of our activities depend on our ability to feel, including simple household chores and negotiating potentially dangerous terrain. In order to create the sensations we experience, the touch information we get with our hands and other body parts travels to the brain. This process has long piqued the interest of scientists.
The roles of the spinal cord and brainstem in receiving, processing, and delivering signals, as well as other important components of touch, are still unknown.
Now, two studies from Harvard Medical School researchers offer significant new insights into how the spinal cord and brainstem affect touch perception.
The study demonstrates that touch signals are actively processed as they pass through the spinal cord and brainstem, which were previously believed to be merely relay centers for touch information.
According to one study, which was published on November 4 in Cell, the brainstem receives information about light touch, such as a hand brush or a kiss on the cheek, via specific neurons in the spinal cord.
Another study, published Nov. 23 in Nature, found that touch processing is shaped by the convergence of direct and indirect touch pathways in the brainstem.
“The spinal cord and brainstem are highlighted in this research as the locations where touch information is combined and processed to express various forms of touch.” “Prior to now, we hadn’t fully understood how these regions contribute to the brain’s representation of pressure, vibration, and other aspects of tactile stimuli,” said David Ginty, the senior author on both papers and the Edward R. and Anne G. Lefler Professor of Neurobiology at the Blavatnik Institute at HMS.
Although the investigations were done on mice, the fundamentals of touch processing may be helpful for researchers looking at human disorders like neuropathic pain, which is characterized by touch dysfunction. Touch mechanisms are substantially conserved across species, including humans.
According to James Gnadt, program director at the National Institute of Neurological Disorders and Stroke (NINDS), which provided some of the funding for the studies, “This detailed understanding of tactile sensation—tthat is, feeling the world through contact with the skin—mmay have profound implications for understanding how disease, disorder, and injury can affect our ability to interact with the environment around us.”
Overlooked and underappreciated
According to the traditional understanding of touch, sensory neurons in the skin respond to touch stimuli like pressure or vibration and transmit this information as electrical impulses that flow straight from the skin to the brainstem. The primary somatosensory cortex, the top level of the touch hierarchy, receives touch information from other nearby neurons and processes it into feeling.
Ginty and his team were uncertain about whether and how the spinal cord and brainstem functioned in the processing of touch signals. These regions, which are at the bottom of the touch hierarchy, work together to create a touch pathway that enters the brain more gradually.
According to Josef Turecek, a postdoctoral fellow in the Ginty lab and the first author on the Nature publication, “People in the field thought that the diversity and richness of touch derived just from sensory neurons in the skin, but that thinking bypasses the spinal cord and brainstem.”
Postsynaptic dorsal column (PSDC) neurons in the spinal cord, which project from the spinal cord into the brainstem, are not well known to many neuroscientists, and textbooks sometimes omit PSDC neurons from diagrams illustrating the specifics of touch, according to Turecek.
The way the spinal cord and brainstem have been disregarded in touch research reminds Ginty of early studies on the vision system. Initially, researchers who studied vision believed that the visual cortex of the brain was where all processing took place. But it turned out that a significant portion of this processing occurs in the retina, which receives visual information well before it reaches the brain.
These two publications examine how touch information from the skin is processed in the spinal cord and brainstem before it proceeds up the touch hierarchy to more complicated brain regions, Ginty said. This is similar to research on the visual system.
Connecting the dots
The researchers recorded the activity of numerous different neurons in the spinal cord at the same time when mice were exposed to various types of touch in the cell study using a method they created. They found that the dorsal horn, the spinal cord’s sensory processing region, had over 90% of its neurons responding to mild touch.
“This was unexpected because it was once believed that the superficial layers of the spinal cord’s dorsal horn neurons mostly responded to painful and warm stimuli. “How light-touch information is transported in the spinal cord is something we hadn’t realized,” Anda Chirila, a research associate in the Ginty lab and the paper’s co-lead author alongside graduate student Genelle Rankin, stated.
Additionally, the dorsal horn’s genetically diverse populations of neurons, which were shown to form a highly interconnected and sophisticated neural network, showed a wide range of reactions to light touch. In turn, this heterogeneity in responses led to a variety of touch information that PSDC neurons sent from the dorsal horn to the brainstem. In fact, the variety of light-touch information transmitted by PSDC neurons was reduced when the researchers silenced different dorsal horn neurons.
We believe that comprehending the basic principles of touch processing requires knowledge of how touch is encoded in the spinal cord, which is the first site in the touch hierarchy.
The brainstem, the next level in the hierarchy of touch, was the focus of the researchers’ other investigation, which was written about in Nature. According to the Cell publication, they investigated the interaction between the direct pathway that transmits touch information from sensory neurons in the skin to the brainstem and the indirect pathway that travels through the spinal cord.
“We were extremely curious about what components of touch each channel brings to the brainstem,” Turecek said. “Brainstem neurons get both direct and indirect information.”
The scientists used mouse brainstem neurons to record the responses as they alternately suppressed each circuit to analyze this query. The results of the studies demonstrated that while the indirect pathway is required to register the intensity of pressure on the skin, the direct pathway is critical for transmitting high-frequency vibration.
“These two paths converge in the brainstem with neurons that can register both vibration and intensity,” Turecek explained, “so you can influence responses of those neurons based on how much direct and indirect input you get.”In other words, brainstem neurons communicate more vibrationally than intensely if they receive more direct input than indirect input, and vice versa.
The scientists also found that the same little patch of skin can transmit touch information via both pathways, with information on intensity traveling down the spinal cord before joining information on vibration, which travels straight to the brainstem. Together, the direct and indirect channels enable the brainstem to create a spatial representation of several touch impulses coming from the same region.
Finally on the map
“Most people have considered the brainstem as a relay station for touch, and they haven’t even had the spinal cord on the map at all,” Ginty added, referring to previous understanding. According to him, the most recent research “shows that a significant amount of information processing is occurring in the spinal cord and brainstem, and that processing is crucial for how the brain depicts the tactile environment.”
He went on to say that this processing is probably a factor in the complexity and variety of touch information that the brainstem transmits to the somatosensory cortex.
To test the results in more realistic settings, Ginty and company intend to repeat the studies in mice that are awake and acting normally. Additionally, they intend to broaden the tests to incorporate more diverse real-world touch sensations, like texture and movement.
The way touch information is processed in the spinal cord and brainstem may be influenced by information from the brain, such as an animal’s level of stress, hunger, or exhaustion. Such information may be especially pertinent for human conditions like autism spectrum disorders or neuropathic pain, in which neural dysfunction results in hypersensitivity to light touch, given that touch mechanisms appear to be conserved across species.
With these investigations, we have established the essential tenets of how these circuits operate and their significance, according to Rankin. Now that we have the means, we can analyze these circuits to learn how they work regularly and what happens when anything goes wrong.
