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

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...

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Bibliographic Details
Published in:	Nature communications Vol. 9; no. 1; pp. 2041 - 15
Main Authors:	櫻井武, Wang Yibing, Cao Liqin, Lee Chia-Ying, Matsuo Tomohiko, Wu Kejia, Asher Greg, Tang Lijun, Saitoh Tsuyoshi, Russell Jamie, Klewe-Nebenius Daniela, Wang Li, Soya Shingo, Hasegawa Emi, Chérasse Yoan, Zhou Jiamin, Li Yuwenbin, Wang Tao, Zhan Xiaowei, Miyoshi Chika, Irukayama Yoko, Cao Jie, Meeks Julian P., Gautron Laurent, Wang Zhiqiang, Sakurai Katsuyasu, Funato Hiromasa, SAKURAI Takeshi, Yanagisawa Masashi, Nagase Hiroshi, Kobayakawa Reiko, Kobayakawa Ko, Beutler Bruce, Liu Qinghua
Format:	Journal Article
Language:	English
Published:	London Nature 23.05.2018 Nature Publishing Group UK Nature Publishing Group Nature Portfolio
Subjects:	13 13/1 13/106 13/109 13/44 14 14/1 14/63 38 38/70 42 45 45/23 631/378/2583 631/378/340 96 Animals Behavior, Animal - physiology Brain Chemical sensors Chemoreceptors Ethyl nitrosourea Fear Fear - physiology Female Footwear Freezing Genetic code Genetics Genotyping Techniques Humanities and Social Sciences Instinct Male Mice Mice, Inbred C57BL Mice, Knockout Molecular chains Molecular modelling multidisciplinary Mutagenesis Neurons - physiology Nociception - physiology Odorant receptors Odorants Odors Pain perception Pungent principles Receptors Science Science (multidisciplinary) Skin Smell Smell - physiology Thiazoles - chemistry Thiazoline Tonic immobility Trigeminal ganglion Trigeminal Ganglion - cytology Trigeminal Ganglion - physiology TRPA1 Cation Channel - physiology Winter
ISSN:	2041-1723, 2041-1723
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Summary:	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
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-018-04324-3