Study Reframes Understanding of How the Nervous System Senses Temperature

For decades, scientists believed the nervous system used different sensory cells to detect warm and cool temperatures. A new study from the Neural Circuits and Behavior Lab at the Max Delbrück Center challenges this assumption, showing that specialized nerve cells in the skin use a single molecular mechanism to signal both directions of temperature change.

Using advanced imaging in mice, researchers led by Phillip Bokiniec and Clarissa Whitmire discovered that most temperature-sensitive nerve cells are activated by cooling and simply reduce their activity when skin warms. “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,” explains Bokiniec. The findings appear in Neuron.

The team developed a novel method to image hundreds of temperature-sensing nerve cells in the spinal sensory ganglia of awake mice. They gently warmed and cooled the animals’ paws while recording individual neuron activity using two-photon microscopy. Importantly, they repeated these experiments in anesthetized mice and observed identical results, proving the anesthetic had no effect on their findings.

The researchers then investigated the molecular basis of temperature sensing by selectively blocking or activating temperature-sensitive ion channels. When they blocked TRPM8, a protein long known as the body’s primary cool sensor, both the response to cooling and the dampening effect of warming disappeared. This revealed that a single molecular sensor generates signals for both temperatures, directly contradicting the traditional view that separate receptors are required for each sensation.

The team created a computer model demonstrating that simply altering TRPM8 activity was sufficient to reproduce the different response patterns observed in their experiments. According to co-author James Poulet, “Scientists have known about these neurons for years, but they were thought to be relatively rare. What surprised us was discovering that they make up most of the temperature-sensing cells.”

These findings have significant implications for understanding sensory disorders. Temperature sensation is essential for daily functioning but becomes disrupted in conditions including neuropathic pain, diabetic neuropathy, chemotherapy-induced nerve damage, and disorders involving abnormal cold sensitivity. “Understanding how healthy temperature sensing works is a prerequisite for understanding what goes wrong in disease,” says Whitmire.

The researchers plan next to investigate how spinal cord processes these signals, how painful temperatures are encoded, and whether these principles apply in humans.