The Cellular Code for Mammalian Thermosensation

Abstract

Mammalian somatosenory neurons respond to thermal stimuli allowing animals to reliably discriminate hot from cold and select their preferred environments. We previously generated mice that are completely insensitive to temperatures from noxious cold to painful heat (−5 to 55 °C) by ablating several different classes of nociceptor early in development. Here we have adopted a selective ablation strategy in adult mice to dissect this phenotype and thereby demonstrated that separate populations of molecularly defined neurons respond to hot and cold. TRPV1-expressing neurons are responsible for all behavioral responses to temperatures between 40 and 50°C, while TRPM8-neurons are required for cold aversion. We also show that more extreme cold and heat activate additional populations of nociceptors including cells expressing Mrgprd. Thus, although eliminating Mrgprd-neurons alone does not affect behavioral responses to temperature, when combined with ablation of TRPV1- or TRPM8-cells, it significantly decreases responses to extreme heat and cold respectively. Notably, ablation of TRPM8-neurons distorts responses to preferred temperatures suggesting that the pleasant thermal sensation of warmth may in fact just reflect reduced aversive-input form TRPM8 and TRPV1-neurons. As predicted by this hypothesis, mice lacking both these classes of thermosensor exhibited neither aversive nor attractive responses to temperatures between 10 and 50 °C. Taken together these results provide a simple cellular basis for mammalian thermosensation whereby two molecularly defined classes of sensory neurons detect and encode both attractive and aversive cues.

Population of sensory neurons essential for asthmatic hyperreactivity of inflamed airways

“…2A and Fig. S2) (26). Our results prove that selective ablation of TRPV1-expressing neurons is sufficient to prevent hyperreactive airway responses (Fig.…”

“…We note that the TRPV1-Cre animals also function as lineage tracers and may express the cre-dependent reporter in adult neurons that are no longer actively expressing TRPV1 (24). This potential difficulty was circumvented by carrying out acute ablations in adult animals via targeted expression of the DTR (26).…”

“…To avoid potential side effects resulting from the loss of sensory neurons during development, we acutely ablated TRPV1-cells in adult animals. In essence, we targeted expression of the DTX receptor (DTR) (25) to TRPV1-cells (TRPV1-DTR) (26) (Fig. 2A) and coupled it with intraperitoneal injections of DTX at a time long after sensory neurons developed but before allergen sensitization with ovalbumin.…”

Neurophysiology of Skin Thermal Sensations

“…The temperature-dependent generation of action potentials in thermo-sensory neurons has been explained by the presence of specific transmembrane proteins which, by gating changes in ion fluxes across the plasma membrane in a temperature-dependent manner, contribute to generating action potentials at the nerve fiber level in response to temperature stimuli (297). Such protein receptors have been recently identified as to belong to the Transient Receptor Potential (TRP) ion channels family (247).…”

Low-cost functional plasticity of TRPV1 supports heat tolerance in squirrels and camels

“…Although both scenarios are simultaneously possible, a somatosensory deficit alone would be sufficient to at least partially diminish temperature sensitivity. Indeed, mice with pharmacologically ablated TRPV1-expressing peripheral nociceptors are unable to discriminate between the wide range of temperatures from 25 to 50°C (13,26). In the case of squirrels, DRG neurons failed to respond to heating from 22 to 46°C, but responded to capsaicin, demonstrating that TRPV1 is expressed and functional in these cells.…”