Summary: Researchers have shown that innocuous temperature perception is encoded predominantly by a single, bidirectional population of peripheral neurons. Using high-resolution, live-tissue imaging in awake mice, the team found that most temperature-sensitive cells are multifunctional: they increase firing during cooling and reduce their baseline activity when the skin warms. These results indicate the brain reads the full range of non-painful temperatures from one shared neural population and a single molecular sensor.
Key Facts
- One population, two directions: Instead of separate neural channels for warm and cool, a dominant group of generalist thermoreceptors signals both cooling and warming.
- Bidirectional baseline coding: Two-photon imaging revealed a simple coding scheme:
- Cooling: Neurons rapidly increase their action potential firing rate.
- Warming: The same neurons suppress or reduce their steady baseline activity.
- Absolute temperature reporting: These neurons encode the actual temperature of the tissue continuously, not only the rate or direction of change, functioning like precise biological thermometers.
- TRPM8 is central: Pharmacological and genetic manipulations showed that removing TRPM8 abolished both the activation to cooling and the suppression during warming, indicating this single ion channel can drive both responses.
- Model confirmation: Computational simulations of TRPM8 kinetics reproduced the full range of firing patterns, supporting that graded changes in one channel explain the observed bidirectional coding.
- Implications for sensory disorders: By clarifying how a healthy system encodes temperature, the findings provide a foundational framework to study and ultimately treat conditions such as neuropathic pain, diabetic neuropathy, and chemotherapy-related sensory damage.
Source: Helmholtz
Specialized nerve endings in the skin continuously report temperature to the brain. For decades, scientists assumed distinct groups of sensory neurons separately encoded non-painful cool and warm stimuli. The new study from the Neural Circuits and Behavior Lab overturns that assumption: most thermoreceptors signal both cooling and warming, using increases or decreases in ongoing activity.
Led by Drs. Phillip Bokiniec and Clarissa Whitmire in Dr. James Poulet’s lab at the Max Delbrück Center, the research combined longitudinal two-photon imaging and targeted manipulations to observe hundreds of sensory neurons in awake mice while their paws were gently warmed and cooled.
“Rather than relying on separate ‘warm’ and ‘cool’ sensors, the nervous system appears to use a single population of cells that signals both directions of temperature change,” says Phillip Bokiniec, co–first author on the study. Using advanced imaging in mice, the authors report in Neuron that most thermoreceptors are activated by cooling and simply decrease their baseline activity when the skin warms. Importantly, these neurons encode absolute temperature values, not merely the speed of temperature change.
The team validated their observations in both awake and anesthetized animals, confirming that anesthesia did not alter the core result. They then applied pharmacological blockers and genetic tools to probe molecular contributors. Blocking or knocking out TRPM8—traditionally described as a “cold” sensor—eliminated both cooling-evoked activation and warming-induced suppression, demonstrating a single molecular channel can govern bidirectional thermal signaling.
Imaging neurons in live mice
To capture population-level dynamics, researchers developed a protocol to monitor L4 dorsal root ganglion neurons in awake mice over time. Two-photon microscopy allowed them to resolve activity in hundreds of cells while delivering controlled thermal stimuli to the paw. The resulting data revealed that although cells responding exclusively to cooling or warming exist, the majority display bidirectional, graded responses tied to absolute temperature.
Complementary computational modeling showed that variation in TRPM8 conductance across neurons could reproduce the diverse response profiles observed experimentally. This supports a parsimonious model: graded adjustments of a single, cool-selective channel account for both increases in firing during cooling and decreases during warming.
Understanding sensory disorders
Accurate temperature sensing is essential for daily behavior and is commonly disrupted by medical conditions such as neuropathic pain, diabetic neuropathy, and chemotherapy-induced nerve damage. Clarifying how healthy temperature encoding operates is a prerequisite for diagnosing and treating these disorders. By pinpointing a unified neural and molecular architecture—one population of thermoreceptors and a central role for TRPM8—this work narrows potential therapeutic targets for restoring balanced thermal perception.
The authors plan to follow up by tracing how these peripheral signals are processed in the spinal cord, investigating the encoding of noxious (painful) temperatures, and exploring whether similar principles apply in humans.
Key Questions Answered:
A: It was a reasonable engineering-style assumption: opposite physical sensations might be encoded by separate, dedicated pathways to avoid ambiguity. Although mixed-response neurons had been observed, they were treated as rare. This study shows those bidirectional neurons are common and form the main temperature-sensing population.
A: Through graded changes in ongoing activity. These neurons maintain a baseline firing rate at neutral temperature. Cooling accelerates that firing; warming suppresses it. The brain interprets higher-than-baseline firing as cold and lower-than-baseline firing as warm.
A: The discovery reframes the search for treatments: instead of separate warm and cold pathways, a single molecular target (TRPM8) and a single neural population may underlie many temperature-sensing disorders. This unified view could guide more precise therapeutic strategies to restore normal thermal sensation.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- Journal paper reviewed in full.
- Additional context added by staff.
About this neuroscience research news
Author: Vera Glasser
Source: Helmholtz
Contact: Vera Glasser – Helmholtz
Image: The image is credited to Neuroscience News
Original Research: Open access. “Population encoding of cool and warm by thermoreceptors” by Clarissa J. Whitmire, James F.A. Poulet, Phillip Bokiniec. Neuron. DOI: 10.1016/j.neuron.2026.06.021
Abstract
Population encoding of cool and warm by thermoreceptors
Innocuous temperature sensation arises from primary afferent thermoreceptors, but how populations of these neurons encode cool and warm remains unresolved. Using two-photon in vivo imaging of the L4 dorsal root ganglion in awake and anesthetized mice, the authors show the thermoreceptor population is strongly biased toward activation by cooling and suppression by warming. While some neurons respond only to cool or warm, most exhibit bidirectional responses and represent absolute temperature in a graded fashion. Pharmacology and computational modeling indicate both activation and suppression could arise from a single cool-selective channel, TRPM8, with diverse profiles explained by differences in TRPM8 conductance. These results support a model where innocuous temperature is largely encoded by one functional class of thermoreceptor via graded, bidirectional activity changes rather than by anatomically and functionally distinct cool and warm cell classes.