Key Questions Answered
Q: What did researchers discover about how we sense cool temperatures?
A: The study identified a complete neural pathway from the skin to the brain dedicated to detecting cool temperatures, showing how this sensation is transmitted and amplified in the spinal cord.
Q: Why is this discovery important?
A: It’s the first time a full temperature-sensing circuit has been mapped, offering insights into basic biology and opening the door to targeted treatments for cold-induced pain, such as that experienced by chemotherapy patients.
Q: How does this pathway differ from cold pain signals?
A: The newly discovered circuit specifically senses harmless coolness and does not mediate painful cold, which likely involves different, more complex pathways.
Summary: A groundbreaking study has mapped the full neural circuit that carries cool temperature signals from the skin to the brain. The pathway begins with molecular sensors in the skin, which activate neurons that send signals to the spinal cord, where the message is amplified before reaching the brain.
This precise circuitry explains how we experience harmless coolness—like stepping into an air-conditioned room—and is distinct from pathways involved in painful cold sensations. Understanding this pathway could lead to new treatments that ease cold-related discomfort without disrupting normal temperature perception.
Key Facts:
- Dedicated Pathway: Researchers identified a complete neural circuit for cool temperature sensing.
- Signal Amplifier: A spinal cord “amplifier” boosts the cool signal en route to the brain.
- Medical Relevance: Findings may help target therapies for cold-induced pain without impairing normal sensation.
Source: University of Michigan
Researchers at the University of Michigan have illuminated a complete sensory pathway showing how the skin communicates the temperature of its surroundings to the brain.
This discovery, believed to be the first of its kind, reveals that cool temperatures get their own pathway, indicating that evolution has created different circuits for hot and cold temperatures.
This creates an elegant solution for ensuring precise thermal perception and appropriate behavioral responses to environmental changes, said Bo Duan, senior author of the new study.
“The skin is the body’s largest organ. It helps us detect our environment and separate, distinguish different stimuli,” said Duan, a U-M associate professor of molecular, cellular, and developmental biology.
“There are still many interesting questions about how it does this, but we now have one pathway for how it senses cool temperatures. This is the first neural circuit for temperature sensation in which the full pathway from the skin to the brain has been clearly identified.”
This work deepens our understanding of fundamental biology and brings us closer to an explanation for how we evolved to inhabit safe temperatures and avoid dangerous extremes, Duan said. But it also has medical implications that can be explored to help improve the quality of life for people in the future.
For example, more than 70% of people who have undergone chemotherapy experience pain caused by cool temperatures, Duan said. The new study found that the neural circuit responsible for sensing innocuous cool does not mediate this type of cold pain.
But, in understanding how the cool-sensing circuitry works when it’s functioning properly under normal conditions, researchers now have a better chance of discovering what goes wrong in disease or injury. It could also help develop targeted therapies that restore healthy sensation without impairing normal temperature perception.
This research was funded by the National Institutes of Health and performed in collaboration with Shawn Xu and his research team in the U-M Life Sciences Institute.
A cool amplifier discovery
In their study, published in the journal Nature Communications, Duan and his team used sophisticated imaging techniques and electrophysiology to observe how mice transmitted the sensation of cool temperatures from their skin to the brain.
It’s an approach the team has applied to other sensations in the past. Headed by postdoctoral research fellow Hankyu Lee and doctoral students Chia Chun Hor and Lorraine Horwitz, the team turned its focus to temperature in this work.
“These tools have allowed us to identify the neural pathways for chemical itch and mechanical itch previously,” Duan said. “Working together, the team identified this very interesting, very dedicated pathway for cool sensation.”
The cool signal starts at the skin, which is home to molecule sensors that can detect a specific range of temperatures between about 15 and 25 degrees Celsius—equivalent to 59 and 77 degrees Fahrenheit. When those sensors engage, they excite primary sensory neurons, which send the cool signal to the spinal cord. Here, the team found that the signal is amplified by specialized interneurons, which then activate projection neurons that connect to the brain.
Researchers had previously known about the skin’s molecular thermometers—they, in part, earned researchers in California the 2021 Nobel Prize in Physiology or Medicine—but the spinal cord’s amplifier was an unknown key ingredient. With the amplifier disabled, the cool signal becomes lost in the noise, the team found.
Although the study was performed in mice, each component of the circuit has been shown to be in humans through genetic sequencing, Duan said. So it’s likely that we have the same pathway to thank for the refreshing sensation of stepping into an air-conditioned room on a hot summer day.
Moving forward, the team is looking to identify the pathway or pathways involved in acute cold pain.
“I think the painful sensations are going to be more complicated,” Duan said. “When we’re in riskier situations, there could be multiple pathways involved.”
His team is also interested in how the brain processes these various skin signals and how we’ve evolved not only to differentiate between them, but also connect emotions with them to help protect ourselves. In fact, it’s the curiosity around those sorts of questions that originally motivated Duan’s work, which he is perpetually reminded of working in Michigan.
“In summer, I love walking along Lake Michigan and having a gentle breeze hit my face. I feel very cool, very comfortable,” Duan said. “But the winter is really terrible for me.”
About this temperature perception and neuroscience research news
Author: Matt Davenport
Source: University of Michigan
Contact: Matt Davenport – University of Michigan
Image: The image is credited to Neuroscience News
Original Research: Open access.
“A dedicated skin-to-brain circuit for cool sensation in mice” by Bo Duan et al. Nature Communications
Abstract
A dedicated skin-to-brain circuit for cool sensation in mice
Perception of external temperature is essential for maintaining homeostasis and avoiding thermal injury. Although molecular thermosensors such as transient receptor potential melastatin type 8 (TRPM8) have been identified, the neural circuits responsible for transmitting cool signals remain unclear.
Here we show that a spinal circuit in mice conveys cool signals from the skin to the brain. Excitatory interneurons in the spinal dorsal horn expressing thyrotropin-releasing hormone receptor (Trhr+) act as a central hub for cool sensation.
These Trhr+ neurons receive monosynaptic input from TRPM8+ sensory afferents and are selectively activated by innocuous cool stimuli. Ablating Trhr+ interneurons abolishes behavioral responses to cool, but not to warm or cold stimuli.
We also identify a population of calcitonin receptor-like receptor-positive (Calcrl+) spinal projection neurons that receive convergent input from both TRPM8+ afferents and Trhr+ interneurons, and transmit cool-specific signals to the lateral parabrachial nucleus (lPBN).
Our findings define a feedforward amplification circuit for cool sensation and reveal a modality-specific spinal pathway for thermal processing.
