When you wrap your hands around a steaming mug of cocoa or dip your toes into a cool bathroom floor, your skin is doing something remarkable: it is talking to your brain about temperature. For more than a hundred years, scientists believed separate groups of nerve cells handled warm and cool sensations. Now, researchers at the Max Delbrück Center in Berlin have discovered the story is far simpler — and more surprising.
Led by Dr. Phillip Bokiniec and Dr. Clarissa Whitmire in the Neural Circuits and Behavior Lab under Dr. James Poulet, the team found that one population of nerve cells does the work of two. "Rather than relying on separate 'warm' and 'cool' sensors, we found that the nervous system appears to use one population of cells that signals both directions of temperature change," said Bokiniec, who now continues this research at the Queensland Brain Institute in Australia.
The researchers developed a technique to watch hundreds of temperature-sensing nerve cells in the spinal cords of awake mice using a powerful imaging method called two-photon microscopy. They gently warmed and cooled the animals' paws while recording the activity of individual nerve cells. The team also tested anesthetized mice and got the same results, proving the anesthesia did not influence their findings.
What they saw shocked them. Most temperature-sensitive nerve cells fire when the skin cools and actually slow down when the skin warms. Scientists had assumed these cells were rare, but they turned out to make up the majority of temperature-sensing cells. The team also showed these cells respond to the actual temperature of the skin, not just how quickly it is changing.
The researchers then blocked or activated specific proteins on the nerve cells. When they blocked a protein called TRPM8 — long known as the body's main cool detector — it eliminated both the response to cooling and the dampening effect that warming has on these cells. A single molecular sensor, it turned out, generates signals for both sensations.
The scientists built a computer model to test their ideas. The model showed that simply changing the activity of TRPM8 was enough to reproduce all the different response patterns they had observed.
For Bokiniec, the findings could eventually help people with conditions where temperature sensing goes wrong, such as diabetic nerve damage or pain from chemotherapy. "Understanding how healthy temperature sensing works is a prerequisite for understanding what goes wrong in disease," said Whitmire.
The team plans next to study how these signals travel through the spinal cord, how painful temperatures are detected, and whether the same principles apply in humans.