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 Russell, Daniela Klewe-Nebenius, Li Wang, Shingo Soya, Emi Hasegawa, Yoan Chérasse, Jiamin Zhou, Yuwenbin Li, Tao Wang, Xiaowei Zhan, Chika Miyoshi, Yoko Irukayama, Jie Cao, Julian P. Meeks, Laurent Gautron, Zhiqiang Wang, Katsuyasu Sakurai, Hiromasa Funato, Takeshi Sakurai, Masashi Yanagisawa, Hiroshi Nagase, Reiko Kobayakawa, Ko Kobayakawa (), Bruce Beutler () and Qinghua Liu ()
Additional contact information
Yibing Wang: National Institute of Biological Sciences
Liqin Cao: University of Tsukuba
Chia-Ying Lee: University of Tsukuba
Tomohiko Matsuo: Kansai Medical University
Kejia Wu: National Institute of Biological Sciences
Greg Asher: University of Tsukuba
Lijun Tang: Kansai Medical University
Tsuyoshi Saitoh: University of Tsukuba
Jamie Russell: University of Texas Southwestern Medical Center
Daniela Klewe-Nebenius: University of Tsukuba
Li Wang: University of Texas Southwestern Medical Center
Shingo Soya: University of Tsukuba
Emi Hasegawa: University of Tsukuba
Yoan Chérasse: University of Tsukuba
Jiamin Zhou: University of Texas Southwestern Medical Center
Yuwenbin Li: University of Texas Southwestern Medical Center
Tao Wang: University of Texas Southwestern Medical Center
Xiaowei Zhan: University of Texas Southwestern Medical Center
Chika Miyoshi: University of Tsukuba
Yoko Irukayama: University of Tsukuba
Jie Cao: University of Texas Southwestern Medical Center
Julian P. Meeks: University of Texas Southwestern Medical Center
Laurent Gautron: University of Texas Southwestern Medical Center
Zhiqiang Wang: University of Tsukuba
Katsuyasu Sakurai: University of Tsukuba
Hiromasa Funato: University of Tsukuba
Takeshi Sakurai: University of Tsukuba
Masashi Yanagisawa: University of Tsukuba
Hiroshi Nagase: University of Tsukuba
Reiko Kobayakawa: Kansai Medical University
Ko Kobayakawa: Kansai Medical University
Bruce Beutler: University of Texas Southwestern Medical Center
Qinghua Liu: National Institute of Biological Sciences

Nature Communications, 2018, vol. 9, issue 1, 1-15

Abstract: 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.

Date: 2018
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-04324-3

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DOI: 10.1038/s41467-018-04324-3

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