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.
| Original language | English (US) |
|---|---|
| Article number | 4324 |
| Journal | Nature Communications |
| Volume | 9 |
| Issue number | 1 |
| DOIs | |
| State | Published - Dec 1 2018 |
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ASJC Scopus subject areas
- Chemistry(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Physics and Astronomy(all)
Cite this
Large-scale forward genetics screening identifies Trpa1 as a chemosensor for predator odor-evoked innate fear behaviors. / Wang, Yibing; Cao, Liqin; Lee, Chia Ying; Matsuo, Tomohiko; Wu, Kejia; Asher, Greg; Tang, Lijun; Saitoh, Tsuyoshi; Russell, Jamie L; 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; Gautron, Laurent; Wang, Zhiqiang; Sakurai, Katsuyasu; Funato, Hiromasa; Sakurai, Takeshi; Yanagisawa, Masashi; Nagase, Hiroshi; Kobayakawa, Reiko; Kobayakawa, Ko; Beutler, Bruce A; Liu, Qinghua.
In: Nature Communications, Vol. 9, No. 1, 4324, 01.12.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Large-scale forward genetics screening identifies Trpa1 as a chemosensor for predator odor-evoked innate fear behaviors
AU - Wang, Yibing
AU - Cao, Liqin
AU - Lee, Chia Ying
AU - Matsuo, Tomohiko
AU - Wu, Kejia
AU - Asher, Greg
AU - Tang, Lijun
AU - Saitoh, Tsuyoshi
AU - Russell, Jamie L
AU - Klewe-Nebenius, Daniela
AU - Wang, Li
AU - Soya, Shingo
AU - Hasegawa, Emi
AU - Chérasse, Yoan
AU - Zhou, Jiamin
AU - Li, Yuwenbin
AU - Wang, Tao
AU - Zhan, Xiaowei
AU - Miyoshi, Chika
AU - Irukayama, Yoko
AU - Cao, Jie
AU - Meeks, Julian
AU - Gautron, Laurent
AU - Wang, Zhiqiang
AU - Sakurai, Katsuyasu
AU - Funato, Hiromasa
AU - Sakurai, Takeshi
AU - Yanagisawa, Masashi
AU - Nagase, Hiroshi
AU - Kobayakawa, Reiko
AU - Kobayakawa, Ko
AU - Beutler, Bruce A
AU - Liu, Qinghua
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85047428032&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-04324-3
DO - 10.1038/s41467-018-04324-3
M3 - Article
C2 - 29795268
AN - SCOPUS:85047428032
VL - 9
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 4324
ER -