Reference - Detail
| RRC ID | 53863 |
|---|---|
| Author | Wang Y, Cao L, Lee CY, Matsuo T, Wu K, Asher G, Tang L, Saitoh T, Russell J, Klewe-Nebenius D, Wang L, Soya S, Hasegawa E, Chérasse Y, Zhou J, Li Y, Wang T, Zhan X, Miyoshi C, Irukayama Y, Cao J, Meeks JP, Gautron L, Wang Z, Sakurai K, Funato H, Sakurai T, Yanagisawa M, Nagase H, Kobayakawa R, Kobayakawa K, Beutler B, Liu Q. |
| Title | Large-scale forward genetics screening identifies Trpa1 as a chemosensor for predator odor-evoked innate fear behaviors. |
| Journal | Nat Commun |
| Abstract |
Innate behaviors are genetically encoded, but their underlying molecular mechanisms remain largely unknown. Predator odor 2,4,5-trimethyl-3-thiazoline (TMT) and its potent analog 2-methyl-2-thiazoline (2MT) are believed to activate specific odorant receptors to elicit innate fear/defensive behaviors in naive mice. Here, we conduct a large-scale recessive genetics screen of ethylnitrosourea (ENU)-mutagenized mice. We find that loss of Trpa1, a pungency/irritancy receptor, diminishes TMT/2MT and snake skin-evoked innate fear/defensive responses. Accordingly, Trpa1 -/- mice fail to effectively activate known fear/stress brain centers upon 2MT exposure, despite their apparent ability to smell and learn to fear 2MT. Moreover, Trpa1 acts as a chemosensor for 2MT/TMT and Trpa1-expressing trigeminal ganglion neurons contribute critically to 2MT-evoked freezing. Our results indicate that Trpa1-mediated nociception plays a crucial role in predator odor-evoked innate fear/defensive behaviors. The work establishes the first forward genetics screen to uncover the molecular mechanism of innate fear, a basic emotion and evolutionarily conserved survival mechanism. |
| Volume | 9(1) |
| Pages | 2041 |
| Published | 2018-5-23 |
| DOI | 10.1038/s41467-018-04324-3 |
| PII | 10.1038/s41467-018-04324-3 |
| PMID | 29795268 |
| PMC | PMC5966455 |
| MeSH | Animals Behavior, Animal / physiology* Fear / physiology* Female Genotyping Techniques Instinct* Male Mice Mice, Inbred C57BL Mice, Knockout Mutagenesis Neurons / physiology Nociception / physiology Odorants Smell / physiology* TRPA1 Cation Channel / physiology* Thiazoles / chemistry Trigeminal Ganglion / cytology Trigeminal Ganglion / physiology |
| IF | 12.121 |
| Times Cited | 4 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | Patent(IFI CLAIMS) |
| Total number of mentions | 18 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | 293T(RCB2202) |