Functional Analysis of Amygdaloid Nucleus by Profiling Activated Neurons

• Project/Area Number: 15K01848
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Brain biometrics
• Research Institution: The University of Tokyo
• Principal Investigator: Kiyama Yuji 東京大学, 先端科学技術研究センター, 特任助教 (90456195)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 扁桃体 / 情動 / 活動神経 / 遺伝子改変動物 / 恐怖 / 透明化 / Arc promoter / Venus / amygdala / arc promoter / GRP / 恐怖条件付け / Arc

Outline of Final Research Achievements

The amygdala is crucially involved in regulation of effects of stress on emotional behavior. GRP(Gastrin-Releasing Pentide) is known stress-activated transmitter. GRP knockout mice exhibited excessive emotional expression only when they were subject to acute stress. To identify the critical neural circuits associated with the emotion, we carried out Arc-reporter mapping by using an Arc-Venus reporter transgenic mouse line. A significant difference was found only in one sub-region of the amygdala, adjecent to the lateral nucleus. These results indicate that the GRP-activated neurons in the nucleus are likely to suppress excessive emotional expression through regulation of downstream circuits.

Academic Significance and Societal Importance of the Research Achievements

日常生活において、適度な心理的ストレスは覚醒レベルを高め、問題や障害の克服に向けた原動力となる。しかし、ストレス耐性が低いと、同じストレスレベルであっても過度な情動反応を引き起こす。そして、それは適応障害等を例に見るとおり生活する上でむしろマイナスに作用することが多い。このような、ストレス下で恐怖・不安等の情動機能を制御して心を平穏に保つための脳神経回路に関しては不明な点が多い。
本研究結果は、ストレス下でも過度な恐怖に苛まれず、適切な行動を選択するための神経回路の一端を明らかにした。今後、部位特異的な神経活動操作を行い、神経回路の詳細な機能解析を進めていく。

Research Products

• [Journal Article] The adhesion molecule cadherin 11 is essential for acquisition of normal hearing ability through middle ear development in the mouse (2018)
  • Author(s): Kiyama Yuji、Kikkawa Yayoi S.、Kinoshita Makoto、Matsumoto Yu、Kondo Kenji、Fujimoto Chisato、Iwasaki Shinichi、Yamasoba Tatsuya、Manabe Toshiya
  • Journal Title: Laboratory Investigation Volume: 98 Issue: 11 Pages: 1364-1374
  • DOI: 10.1038/s41374-018-0083-y
  • Peer Reviewed / Open Access
• [Journal Article] Emerging roles of ARHGAP33 in intracellular trafficking of TrkB and pathophysiology of neuropsychiatric disorders (2016)
  • Author(s): Nakazawa T, Hashimoto R, Sakoori K, Sugaya Y, Tanimura A, Hashimotodani Y, Ohi K, Yamamori H, Yasuda Y, Umeda-Yano S, Kiyama Y, Konno K, Inoue T, Yokoyama K, Inoue T, Numata S, Ohnuma T, Iwata N, Ozaki N, Hashimoto H, Watanabe M, Manabe T, Yamamoto T, Takeda M, Kano M.
  • Journal Title: Nat Communications Volume: 7 Issue: 1 Pages: 10594-10594
  • DOI: 10.1038/ncomms10594
  • NAID: 120006535052
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] GRP regulates fear learning under stress conditions (2016)
  • Author(s): 後藤史子、城山優治、 小川糸音、奥野浩行、吉田進昭、尾藤晴彦、真鍋俊也
  • Organizer: 日本神経科学学会大会
  • Place of Presentation: パシフィコ横浜
• [Remarks] 東京大学医科学研究所 基礎医科学部門 神経ネットワーク分野
  • URL: http://www.ims.u-tokyo.ac.jp/NeuronalNetwork/Neuronal_Network/Index_japanese.htm