Researchers in the lab of James Poulet have uncovered how the nervous system senses cool and warm temperatures. The findings, published in Neuron challenge a long-standing view of temperature sensing and could guide future research into pain and sensory disorders.
Whether we hold a warm mug or step onto a cool floor, specialized nerve cells in the skin constantly report temperature to the brain. Scientists have long assumed that separate groups of sensory cells detect non-painful cool and warm temperatures. Now researchers led by Drs. Phillip Bokiniec and Clarissa Whitmire in the Neural Circuits and Behavior Lab of Dr. James Poulet at the Max Delbrück Center have found that this assumption is too simplistic.
"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, who shares first authorship of the study with Whitmire. Bokiniec is a now researcher in the Sensory Neural Coding lab of Dr. Clarissa Whitmire at the Queensland Brain Institute.
Using advanced imaging in mice, the team report in "Neuron" that most temperature-sensitive nerve cells are activated by cooling, and merely reduce their activity when the skin warms. The researchers also showed that these cells react to the actual temperature of the skin rather than simply detecting how much it has changed. This finding reshapes scientists' understanding of one of the body's most fundamental senses.
"Scientists have known about these neurons for years," notes Poulet, "but they were thought to be relatively rare. What surprised us was discovering that they make up most of the temperature-sensing cells."
Imaging neurons in live mice
The researchers developed a method to image hundreds of temperature-sensing nerve cells in the spinal sensory ganglia of awake mice over time. They gently warmed and cooled the animals' paws while recording the activity of individual neurons using two-photon microscopy. They also performed this experiment in anesthetized mice and found the same result. This proved that that the anesthetic itself did not affect their results.
The team then selectively blocked or activated temperature-sensitive ion channels. Blocking the protein TRPM8 — long known as the body's main sensor for detecting cool temperatures — eliminated both the response to cooling and the dampening effect that warming has on these nerve cells. This showed that a single molecular sensor can generate signals for both cool and warm, challenging the traditional view that separate receptors are needed for each sensation.
The team also developed a computer model to test their hypothesis. It showed that simply changing the activity of a TRPM8 was enough to reproduce the different response patterns seen in the experiments.
Understanding sensory disorders
Temperature sensation is essential for everyday life, but it is also disrupted in many medical conditions, including neuropathic pain, diabetic neuropathy, chemotherapy-induced nerve damage and disorders that cause abnormal sensitivity to cold. "Understanding how healthy temperature sensing works is a prerequisite for understanding what goes wrong in disease," says Whitmire.
The researchers next plan to investigate how these signals are processed in the spinal cord, how painful temperatures are encoded, and whether the same principles apply in humans.
Max Delbrück Center
The Max Delbrück Center for Molecular Medicine in the Helmholtz Association lays the foundation for the medicine of tomorrow through today's discoveries. At locations in Berlin-Buch, Berlin-Mitte, Heidelberg, and Mannheim, interdisciplinary teams investigate the complexity of disease at the systems level – from molecules and cells to organs and entire organisms. Together with academic, clinical, and industry partners, and as part of global networks, we turn biological insights into innovations for early detection, personalized therapies, and disease prevention. Founded in 1992, the Max Delbrück Center is home to a vibrant, international research community of around 1,800 people from over 70 countries. We are 90 percent funded by the German federal government and 10 percent by the state of Berlin.
