Two top journals in a row, revealing surprising new roles for the spinal cord and brainstem in touch

The sense of touch is essential to almost everything we do, from routine tasks at home to navigating
unfamiliar terrain that can hide dangers.
Scientists have long wondered how touch information we get with our hands and other parts of our body gets into the brain to produce our sensations
.
However, 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 papers by scientists at Harvard Medical School have revealed key new insights
into how the spinal cord and brainstem affect touch.
Specifically, the study showed that the spinal cord and brainstem, previously thought to be just relay centers for touch information, are actively involved in processing touch signals
as they are transmitted to higher-order brain regions.

A study published Nov.
4 in the journal Cell showed that special neurons in the spinal cord form a complex network that processes light touches — such as a swipe of a hand or a peck on the cheek — and sends this information to the brainstem
.
Now, in another study, published Nov.
23 in the journal Nature, researchers have found that direct and indirect contact pathways work together to converge in the brainstem to form the way
touch is processed.

"These studies focused on the spinal cord and brainstem, where touch information is integrated and processed to deliver different types of touch
.
Until now, we didn't fully understand how these regions affect the brain's behavior in response to vibration, stress, and other features of tactile stimuli," said David Ginty, the Edward R.
and Anne G.
Lefler Professor of Neurobiology at the HMS Blavatnik Institute and senior author
of both papers.

Although these studies were conducted in rodents, the mechanisms of touch are largely cross-species-conserved, including in humans, suggesting that the basics of touch processing could be useful to scientists studying human conditions, such as neuropathic pain
characterized by touch dysfunction.

James Gnadt, program director at the National Institute of Neurological Disorders and Stroke (NINDS), said: "This detailed understanding of touch — that is, feeling the world through contact with skin — could have profound implications
for understanding how diseases, disorders and injuries affect our ability to interact with our surroundings.
"

Neglected and undervalued

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

However, Ginty and his team wanted to know if and how the spinal cord and brainstem were involved in processing touch information
.
These areas occupy the lowest level of the touch hierarchy and combine to form a more indirect touch channel
into the brain.

"People in the field think that the diversity and abundance of touch comes only from sensory neurons on the skin, but this thinking bypasses the spinal cord and brainstem," said Josef Turecek, a postdoc in Ginty's lab and lead author
of the paper in the journal Nature.

Many neuroscientists are unfamiliar with spinal cord neurons, called posterior synaptic column (PSDC) neurons, which project from the spinal cord to the brainstem, and textbooks tend to exclude PSDC neurons from diagrams describing touch details, Turecek explains
.

For Ginty, the way the spinal cord and brainstem are overlooked in touch is reminiscent of earlier studies of
the visual system.
Initially, scientists who study vision believed that all processing took place in the visual cortex of the brain
.
However, it turns out that the retina accepts visual information before it reaches the cerebral cortex, and it is involved in a lot in
processing this information.

"Similar to the study of the visual system, these two papers explore how touch information from the skin is processed in the spinal cord and brainstem before moving up to more complex brain regions
," Ginty said.

Connect the dots

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

"This is surprising because it has traditionally been thought that dorsal horn neurons in the superficial layers of the spinal cord respond
primarily to temperature and painful stimuli.
We haven't yet realized how light-touch information is distributed across the spinal cord," said Anda Chirila, a researcher in Ginty's lab who co-authored the paper
with graduate student Genelle Rankin.

In addition, these responses to light touch varied widely between genetically distinct populations of neurons in the dorsal horn, which were found to form a highly interconnected and complex neural network
.
This change in response, in turn, leads to the diversity of touch information transmitted from the dorsal horn to the
brainstem by PSDC neurons.
In fact, when the researchers silenced various dorsal-horned neurons, they saw a reduced
diversity of light contact information transmitted by PSDC neurons.

"We think that information about how touch is encoded in the spinal cord is important for understanding fundamental aspects of touch processing," Chirila said
.
The spinal cord is the first site
in the hierarchy of touches.

In another study they published in the journal Nature, the scientists focused on the next step in the touch hierarchy: the brainstem
.
They explored the relationship between direct pathways from sensory neurons in the skin to the brainstem and indirect pathways that send touch information through the spinal cord, as described in the Cell paper
.

Turecek said: "Brainstem neurons can get direct and indirect input, and we were really curious to see how touching each pathway affects
the brainstem.
"

To resolve this question, the researchers alternately silenced each pathway and recorded the responses
of mouse brainstem neurons.
Experiments have shown that the direct pathway is important for transmitting high-frequency vibrations, while the indirect pathway requires encoding
the stress intensity on the skin.

"The idea is that these two pathways converge in the brainstem with neurons that can encode vibration and intensity, so you can shape the responses
of those neurons based on how much direct and indirect input you have," Turecek explains.
In other words, if brainstem neurons have more direct input than indirect input, they transmit more vibrations than intensity, and vice versa
.

In addition, the team found that both pathways can transmit touch information from the same small area of skin, with intensity information bypassing the spinal cord and then combining with vibration information to pass directly to the brainstem
.
In this way, direct and indirect pathways work together to allow the brainstem to form spatial representations
of different types of touch stimuli from the same region.

The truth emerges

So far, "most people think of the brainstem as a relay station for the sense of touch, and they don't even see the spinal cord on a map at all," Ginty said
.
For him, the new study "demonstrates that there is a lot of information processing in the spinal cord and brainstem, and that processing is critical
to how the brain presents the tactile world.
" ”

He added that this processing may contribute to the complexity and diversity
of touch information sent by the brainstem to the somatosensory cortex.

Next, Ginty and his team plan to repeat these experiments in awake and behavioral mice, testing the findings
under more natural conditions.
They also want to expand the scope of the experiment to include more types of real-world touch stimuli, such as texture and movement
.

The researchers were also interested in how information from the brain, such as levels of stress, hunger or exhaustion in animals, 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 type of information may be particularly relevant in human conditions, such as autism spectrum disorder or neuropathic pain, where neurological dysfunction leads to an oversensitivity
to light touch.

"Through these studies, we have laid down the basic building blocks of how these circuits work and why they are important," Rankin said
.
"Now we have the tools to dissect these circuits to understand how they work properly and what changes
when something goes wrong.
"

Anda M.
Chirila et al, Mechanoreceptor signal convergence and transformation in the dorsal horn flexibly shape a diversity of outputs to the brain, Cell (2022).