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
Resource
Human and Animal Cells 293T(RCB2202)