How the Skin Distinguishes Cool from Warm
Researchers in the lab of Dr. James Poulet at the Max Delbrück Center have shown how the nervous system tells cool and warm temperatures apart, overturning a long-held assumption in sensory biology.
Skin constantly reports temperature to the brain, whether it's the warmth of a mug in hand or the coolness of a floor underfoot. For decades, scientists assumed that separate populations of nerve cells were responsible for sensing non-painful warmth and coolness. A team led by Drs. Phillip Bokiniec and Clarissa Whitmire in Poulet's Neural Circuits and Behavior Lab has now found that this picture is oversimplified: a single population of sensory neurons appears to signal both directions of temperature change, rather than warmth and cold being handled by dedicated, separate sensors. The results of the study were recently published in the journal Neuron.
Watching temperature sensing in real time
To track this, the team built a method for imaging hundreds of temperature-sensitive nerve cells in the spinal sensory ganglia of awake mice, using two-photon microscopy to record individual neurons as the animals' paws were gently warmed and cooled. The same experiment repeated in anesthetized mice produced matching results, ruling out the anesthetic as a confounding factor.
The recordings showed that most of these temperature-sensing neurons fire in response to cooling, and simply quiet down as the skin warms, rather than being driven by two separate populations tuned to opposite directions of change. The cells also tracked the skin's actual temperature rather than only the rate at which it changed.
One molecular sensor, two signals
The researchers then manipulated temperature-sensitive ion channels directly. Blocking TRPM8, the protein long identified as the primary detector of cool temperatures, wiped out both the neurons' response to cooling and their reduced firing during warming. That result pointed to a single molecular sensor driving signals for both warm and cool, rather than requiring distinct receptors for each. A computer model built by the team reproduced the same response patterns simply by varying TRPM8 activity, reinforcing the finding. As Poulet put it, these neurons had long been assumed to be uncommon, when in fact they turned out to make up the majority of temperature-sensing cells.
Relevance for pain and sensory disorders
Temperature sensing goes awry in a range of conditions, including neuropathic pain, diabetic neuropathy, chemotherapy-induced nerve damage, and disorders involving abnormal cold sensitivity. Whitmire noted that establishing how normal temperature sensing works is a necessary step toward understanding what breaks down in these disorders. The team's next steps include examining how these signals are processed in the spinal cord, how the nervous system encodes painfully hot or cold temperatures, and whether the same mechanism holds true in humans.
Source: Max Delbrück Center Press
Contact:
Prof. Dr. James Poulet
Max Delbrück Center for Molecular Medicine (MDC)
Neural Circuits and Behavior Lab
Robert-Rössle-Straße 10 13125 Berlin