1. The cellular code for mammalian thermosensation.
- Author
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Pogorzala LA, Mishra SK, and Hoon MA
- Subjects
- Animals, Avoidance Learning drug effects, Avoidance Learning physiology, Body Temperature drug effects, Cell Count, Choice Behavior drug effects, Choice Behavior physiology, Cold Temperature, Diphtheria Toxin toxicity, Escape Reaction drug effects, Escape Reaction physiology, Ganglia, Spinal cytology, Gene Expression Regulation drug effects, Gene Expression Regulation genetics, Green Fluorescent Proteins genetics, Heparin-binding EGF-like Growth Factor, Hot Temperature adverse effects, Intercellular Signaling Peptides and Proteins genetics, Mice, Mice, Transgenic, Mutation genetics, Poisons toxicity, Reaction Time drug effects, Reaction Time genetics, Receptors, G-Protein-Coupled genetics, Receptors, G-Protein-Coupled metabolism, Sensory Receptor Cells drug effects, TRPM Cation Channels genetics, TRPV Cation Channels genetics, Thermosensing drug effects, Thermosensing genetics, Body Temperature genetics, Gene Expression Regulation physiology, Sensory Receptor Cells physiology, Thermosensing physiology
- Abstract
Mammalian somatosenory neurons respond to thermal stimuli and allow animals to reliably discriminate hot from cold and to select their preferred environments. Previously, we 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. In the present study, we have adopted a selective ablation strategy in adult mice to study this phenotype and have 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, whereas 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. Therefore, 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. 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 from TRPM8 and TRPV1 neurons. As predicted by this hypothesis, mice lacking both classes of thermosensor exhibited neither aversive nor attractive responses to temperatures between 10 and 50°C. Our 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.
- Published
- 2013
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