Large-scale forward genetics screening identifies Trpa1 as a chemosensor for predator odor-evoked innate fear behaviors

Yibing Wang, Liqin Cao, Chia Ying Lee, Tomohiko Matsuo, Kejia Wu, Greg Asher, Lijun Tang, Tsuyoshi Saitoh, Jamie L Russell, Daniela Klewe-Nebenius, Li Wang, Shingo Soya, Emi Hasegawa, Yoan Chérasse, Jiamin Zhou, Yuwenbin Li, Tao Wang, Xiaowei Zhan, Chika Miyoshi, Yoko IrukayamaJie Cao, Julian Meeks, Laurent Gautron, Zhiqiang Wang, Katsuyasu Sakurai, Hiromasa Funato, Takeshi Sakurai, Masashi Yanagisawa, Hiroshi Nagase, Reiko Kobayakawa, Ko Kobayakawa, Bruce A Beutler, Qinghua Liu

Research output: Contribution to journalArticlepeer-review

41 Scopus citations


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.

Original languageEnglish (US)
Article number2041
JournalNature communications
Issue number1
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology
  • General Physics and Astronomy


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