Unexpected Function of Spinal Cord and Brainstem in Processing Touch Signals to Brain Discovered by Harvard Scientists

A recent study has shown that the brainstem and spinal cord are vital in transmitting touch signals to the brain. Our sense of touch is crucial for various activities, from everyday tasks to challenging environments. Scientists have always been interested in understanding how to touch sensations are generated in the brain, but there are still many unknowns about how the spinal cord and brainstem contribute to receiving, processing, and transmitting touch signals.

Harvard researchers have conducted two studies that have greatly expanded our understanding of the role of the spinal cord and brainstem in touch. The studies showed that these structures, previously thought to pass on touch information, are involved in processing touch signals as they are transmitted to other brain parts.

One of the studies, published in the journal Cell, found that specialized neurons in the spinal cord form a network that processes light touch sensations (such as a gentle brush or a kiss on the cheek) and sends this information to the brainstem. These findings suggest that the spinal cord and brainstem have a more complex role in touch processing than previously thought.

In another study published in the journal Nature, the researchers found that direct and indirect touch pathways work together and meet in the brainstem to influence how touch is processed. These studies highlight the spinal cord and brainstem as key areas where touch information is integrated and processed to convey various types of touch. These findings suggest that the spinal cord and brainstem have a more important role in touch processing than previously believed.

Unappreciated and Overseen Initial Analysis

David Ginty, the senior author on both studies, and Edward R. and Anne G. Lefler, Professor of Neurobiology at Harvard Medical School, stated that these studies show how the spinal cord and brainstem contribute to the brain's representation of touch sensations such as vibration and pressure. Although the studies were conducted in mice, touch mechanisms are similar across species, including humans. These findings may be relevant for scientists studying touch dysfunction in human conditions such as neuropathic pain.

James Gnadt, program director at the National Institute of Neurological Disorders and Stroke, which partially funded the studies, said that this new understanding of touch sensation might have significant consequences for understanding how illness, disorders, and injuries can impact our ability to interact with our surroundings.

Traditionally, it was believed that when the skin is touched by something (such as pressure or vibration), sensory neurons in the skin send electrical impulses directly to the brainstem to be transmitted to the primary somatosensory cortex (the highest level of the touch hierarchy) for processing into sensation. However, the researchers from Harvard Medical School questioned whether and how the spinal cord and brainstem are involved in processing touch information. These structures are located at the lower level of the touch hierarchy and form an indirect pathway into the brain.

Many neuroscientists are unaware of spinal cord neurons called postsynaptic dorsal column (PSDC) neurons that project from the spinal cord into the brainstem. These neurons are often not included in diagrams of touch pathways in textbooks. Josef Turecek, a postdoctoral fellow in the Ginty lab and the first author of the Nature paper, explained that it was previously thought that the diversity and richness of touch sensations came solely from sensory neurons in the skin, but this view ignores the role of the spinal cord and brainstem.

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New research suggests spinal cord and brainstem are essential for processing touch signals as they travel to the brain.

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Linking the Studies

Ginty compared the previously overlooked role of the spinal cord and brainstem in touch processing to early research on the visual system. Initially, scientists believed that all visual processing occurred in the visual cortex of the brain, but later it was discovered that the retina (which receives visual information before it reaches the cortex) is also heavily involved in processing this information. Similarly, these two studies show how information from the skin is processed in the spinal cord and brainstem before it is transmitted to higher-level brain regions. This highlights the importance of these lower-level structures in touch processing.

In the study published in Cell, the researchers used a technique they developed to record the activity of many different neurons in the spinal cord as mice experienced various types of touch. They found that over 90% of neurons in the spinal cord's dorsal horn (the sensory processing area) responded to light touch. This was surprising because it was previously thought neurons in the dorsal horn's superficial layers mainly responded to temperature and painful stimuli. The researchers were surprised to discover how light touch information is distributed in the spinal cord. Anda Chirila, a research fellow in the Ginty lab and the co-lead author on the paper with graduate student Genelle Rankin, said that this finding highlights the complexity of touch processing in the spinal cord.

The researchers also found that the responses to light touch varied significantly among different populations of neurons in the dorsal horn, which formed a complex neural network. This variation in responses led to a diverse range of touch information transmitted from the dorsal horn to the brainstem by PSDC neurons. When the researchers silenced certain neurons in the dorsal horn, they observed a reduction in the diversity of light touch information conveyed by the PSDC neurons.

Chirila said that this information about how touch is encoded in the spinal cord (the first level in the touch hierarchy) is important for understanding the fundamental processes of touch processing. In their other study published in Nature, the scientists focused on the next level of the touch hierarchy: the brainstem. They examined the relationship between the direct pathway from sensory neurons in the skin to the brainstem and the indirect pathway that sends touch information through the spinal cord (as described in the Cell paper). Turecek said that brainstem neurons receive both direct and indirect input, and the researchers were curious about which aspects of touch each pathway brings to the brainstem.

Creating the Brain Map

To better understand the role of each pathway, the researchers silenced one pathway at a time and recorded the response of neurons in the mouse brainstems. The experiments showed that the direct pathway is important for transmitting high-frequency vibrations, while the indirect pathway is necessary for encoding the intensity of pressure on the skin. Turecek explained that the idea is that these two pathways come together in the brainstem with neurons that can encode both vibration and intensity. This means that the response of these neurons can be shaped by the balance of direct and indirect input they receive.

For example, if brainstem neurons receive more direct input than indirect input, they will convey more vibration than intensity and vice versa. The researchers also found that both pathways can transmit touch information from the same small area of skin, with information on intensity traveling through the spinal cord before merging with information on the vibration that travels directly to the brainstem. In this way, the direct and indirect pathways work together to enable the brainstem to create a spatial representation of different touch stimuli from the same area.

Ginty stated that until now, most people have viewed the brainstem as just a relay station for touch and have not considered the spinal cord's role. He believes that the new studies demonstrate a significant amount of information processing in the spinal cord and brainstem, which is critical for how the brain interprets touch sensations. This processing likely contributes to the complexity and diversity of the touch information that the brainstem sends to the somatosensory cortex. In the future, the researchers plan to repeat the experiments in mice that are awake and behaving to test the findings under more natural conditions.

They also want to include more real-world touch stimuli, such as texture and movement, in the experiments. The researchers are also interested in how information from the brain (such as stress, hunger, or fatigue) affects touch processing in the spinal cord and brainstem. Given that touch mechanisms are similar across species, this information may be particularly relevant for human conditions such as autism spectrum disorders or neuropathic pain, in which neural dysfunction causes heightened sensitivity to light touch. Rankin said that these studies had laid the foundation for understanding how these circuits work and their importance, and now the researchers have the tools to study these circuits to understand how they function normally and what changes when something goes wrong.