Elucidate the molecular mechanisms of innate fear and its relation to mental disorders

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K08133
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Integrative animal science
• Research Institution: University of Tsukuba
• Principal Investigator: Cao Liqin 筑波大学, 国際統合睡眠医科学研究機構, 助教 (60399475)
• Co-Investigator(Kenkyū-buntansha): クレウエ・ネベニウス ダニエラ 筑波大学, 国際統合睡眠医科学研究機構, 研究員 (60737667)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 先天的恐怖 / 恐怖感情 / 精神疾患

Outline of Final Research Achievements

Irrational fears are linked to a variety of mental illnesses. However, the molecular mechanisms of fear remain largely unknown. To this end, we conducted a novel predator odor-based “innate fear” forward genetic screen of ethylnitrosourea (ENU)-mutagenized mice, and identified a recessive mutation in Trpa1 gene that led to diminished innate fear responses and a dominant mutation that led to an abnormal fear response, jumping phenotype (hence named Popcorn mutant), upon predator odor exposure. By using a host of biochemical, cellular, neuroscience and behavior assays, we demonstrated that Trpa1 functions as a novel chemosensor for predator odors and Trpa1-expressing trigeminal ganglion (TG) neurons contribute critically to predator odor-evoked innate fear/defense behaviors. We found that Popcorn mutation causes schizophrenia-like behaviors in mice.

Free Research Field

動物生命科学

Academic Significance and Societal Importance of the Research Achievements

We established the first forward genetics screen to uncover the molecular mechanism of fear, a basic emotion that is inextricably linked with mental health. The results have the potential to contribute greatly to developing medicines and therapeutic interventions for fear-related mental disorders.