title: The cellular code for mammalian thermosensation.
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.
authors.affiliation: Molecular Genetics Unit, Laboratory of Sensory Biology, National Institute of Dental and Craniofacial Research-National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Leah A
authors.initials: LA
authors.lastname: Pogorzala
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Mishra
authors.forename: Mark A
authors.initials: MA
authors.lastname: Hoon
mesh_terms: D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001831:Body Temperature / Q000187:drug effects / Q000235:genetics*; D002452:Cell Count; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D003080:Cold Temperature; D004167:Diphtheria Toxin / Q000633:toxicity; D004924:Escape Reaction / Q000187:drug effects / Q000502:physiology; D005727:Ganglia, Spinal / Q000166:cytology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D066257:Heparin-binding EGF-like Growth Factor; D006358:Hot Temperature / Q000009:adverse effects; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics; D011042:Poisons / Q000633:toxicity; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000502:physiology*; D050053:TRPM Cation Channels / Q000235:genetics; D050916:TRPV Cation Channels / Q000235:genetics; D013697:Thermosensing / Q000187:drug effects / Q000235:genetics / Q000502:physiology*
chemical_list: D004167:Diphtheria Toxin; C587884:Hbegf protein, mouse; D066257:Heparin-binding EGF-like Growth Factor; D036341:Intercellular Signaling Peptides and Proteins; C497098:Mrgprd protein, mouse; D011042:Poisons; D043562:Receptors, G-Protein-Coupled; D050053:TRPM Cation Channels; C492297:TRPM8 protein, mouse; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D049452:Green Fluorescent Proteins
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