2019 Fiscal Year Annual Research Report
Elucidate the molecular mechanisms of innate fear and its relation to mental disorders
| Project/Area Number |
17K08133
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| Research Institution | University of Tsukuba |
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Principal Investigator |
曹 麗琴 筑波大学, 国際統合睡眠医科学研究機構, 助教 (60399475)
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| 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)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | 先天的恐怖 / 恐怖感情 / 精神疾患 |
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| Outline of Annual Research Achievements |
Fear is a basic emotion that enhances animal survival by triggering appropriate defensive responses (e.g. freeze, fight or flight) to perceived danger. However, irrational fears are linked to a variety of mental illnesses, such as phobia, anxiety, depression, PTSD etc. The molecular mechanisms of fear remain largely unknown. We conducted a novel predator odor (2MT/TMT)-based “innate fear” forward genetic screen of ethylnitrosourea (ENU)-mutagenized mice, and identified that loss of transient receptor potential A1 (Trpa1) diminishes predator odor-evoked innate fear/defensive responses. We demonstrated that Trpa1 functions as a novel chemosensor for 2MT/TMT, and that Trpa1-expressing trigeminal ganglion (TG) neurons contribute critically to 2MT-induced innate freezing behavior. The results are published in Nature Communications 9, 2041 (2018). Besides defensive behaviors, fear also evokes physiological responses, such as regulations of body temperature, heart rate and blood pressure, to enhance animal survival. We investigated the neural mechanism of 2MT-evoked innate fear-associated thermoregulation using brain c-fos mapping, chemogenetic and optogenetic approaches. We have made interesting findings, and the results have been submitted to a high-profile journal for publication.
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