A new study led by scientists from the University of Pennsylvania, Karolinska Institutet, and Linköping University has revealed a landscape view of the human sense of touch.
Somatosensory diversity arises from heterogeneous dorsal root ganglion (DRG) neurons. However, the cell body transcriptome, a key piece of information for deciphering the function of individual human (h)DRG neurons, is lacking due to technical difficulties. In a new study, Yu others. They isolated somatic cells from individual hDRG neurons and performed deep RNA sequencing (RNA-seq) to detect an average of more than 9,000 unique genes per neuron, identifying 16 types of neurons.
Humans perceive touch, temperature, and pain through the somatosensory system.
The general understanding is that there are specific types of neurons for each type of emotion, such as pain, pleasant touch, or coldness.
But new research casts doubt on that notion and shows that bodily sensations are probably much more complex than that.
“Much of the knowledge we have today about how the nervous system works comes from studies of animals,” said Dr. Wenqing Luo of the University of Pennsylvania and colleagues.
“But how similar are mice and humans, for example?”
“Many discoveries made in animal studies have not been confirmed in human studies.”
“One reason for this may be a lack of understanding of how it works in the human body.”
“We wanted to create a detailed atlas of the different types of neurons involved in somatosensation in humans and compare it with neurons in mice and the primate macaque.”
The study involved a detailed analysis of the genes used by individual neurons, so-called deep RNA sequencing.
Neurons with similar gene expression profiles were grouped as one sensory neuron type.
In this way, the researchers identified 16 unique human neuron types.
This study is the first to link gene expression and actual function in different types of neurons.
To investigate the function of neurons, the scientists used microneurography techniques to listen to the signals of one neuron at a time.
Using this technique, skin neurons in awake participants are exposed to temperature, touch, or certain chemicals, and individual neurons are “listened in” to determine how those particular neurons respond and send signals to the brain. You can find out if it is.
During these experiments, the authors made discoveries that would not have been possible if mapping the cellular machinery of different types of neurons had not given them new ideas for experiments.
One such discovery concerns a type of neuron that responds to pleasant touch.
The researchers discovered that this cell type unexpectedly responded to heat and also to capsaicin, the chemical that gives chili peppers their heat.
Scientists were surprised that the touch-sensing neurons responded to such stimuli, since their response to capsaicin is typical of pain-sensing neurons.
Additionally, this type of neuron also responded to cooling, even though it does not produce the only protein known to date that signals the perception of cold.
This finding cannot be explained by what is known about cellular mechanisms and suggests that there are other mechanisms for detecting colds that have yet to be discovered.
The authors speculate that these neurons form an integrated sensory pathway that produces pleasurable sensations.
“We have been listening to the neural signals from these neurons for 10 years, but we knew nothing about their molecular characteristics,” said Dr. Håkan Ólausson from Linköping University.
“This study shows us what kinds of proteins these neurons express and what kinds of stimuli they can respond to, and we can now make connections between them. Moving forward.”
Another example is a type of pain-sensing neuron that conducts very rapidly and has been shown to respond to non-painful cooling and menthol.
“There is a common understanding that neurons are very specialized: one type of neuron detects cold, another type detects specific vibrational frequencies, a third type responds to pressure, and so on.” said Dr. Saad Nagy, also from Linköping University.
“That's how people often talk about it. But it turns out it's much more complicated than that.”
So how do mice, macaques, and humans compare? How similar are we? Many of the 16 types of neurons the researchers identified in their study are largely similar across species.
The biggest difference they found was that conduction in pain-sensing neurons was much faster in response to stimuli that could cause injury.
Compared to mice, humans have more pain neurons, a type of neuron that sends pain signals to the brain at high speeds.
“Our study doesn't answer why this is the case, but we have a theory,” Dr. Ólausson said.
“The fact that pain signals are emitted at a much faster rate in humans compared to mice is probably just a reflection of their body size.”
“Mice don't need such rapid neural signaling. But in humans, the distances are longer and the signals need to be sent to the brain more quickly, before reacting and withdrawing.” You will be injured.”
Regarding this research, paper in diary natural neuroscience.
_____
H. Yu others. Utilizing deep sequencing of single cell somatic RNA to explore the neural basis of human somatosensation. nut neurosipublished online on November 4, 2024. doi: 10.1038/s41593-024-01794-1
