Analysis of neural functions by optical manipulation of calcineurin

• Project/Area Number: 17K13270
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Basic / Social brain science
• Research Institution: The University of Tokyo
• Principal Investigator: Fujii Hajime 東京大学, 大学院医学系研究科(医学部), 助教 (80717546)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
• Keywords: 蛍光イメージング / 神経可塑性 / Ca2+シグナリング / 光操作 / シナプス可塑性 / 神経機能 / カルシウムシグナル / リン酸化シグナル / 神経科学 / シグナル伝達 / イメージング

Outline of Final Research Achievements

Calcineurin plays important roles in memory and learning. In order to understand how it works to realize higher brain function, it is necessary to develop methods to visualize and manipulate its mobility and its enzymatic activity in living neurons. In this study, we visualized the movement of calcineurin and CaMKII molecules and measured their activities while performing optical manipulations by our improved method that has higher spatial and temporal resolutions. Using them, we measured the difference in the activity of calcineurin and CaMKII when synaptic structure is manipulated by artificial light stimulation. These result provides insights to unveil biochemical signaling rules that underlie higher brain functions such as learning and memory.

Academic Significance and Societal Importance of the Research Achievements

本研究によって、生きた神経細胞のシナプスや樹状突起で、カルシニューリンの動きやその活性が時間とともに強くなったり弱くなっていく様子を動画として捉えることに成功し、世界に先駆けた成果が得られました。これは、記憶や学習といった高次脳機能のメカニズムを理解するうえ重要なものとなります。また、カルシニューリンは、高次脳機能をはじめ、免疫系や循環器系など全身における生理や病態に非常に重要な役割を果たしています。今後、本研究の手法を発展させることで、これら病態を細胞レベルで理解する道筋ができてゆくと考えられます。

Research Products

• [Journal Article] A Critical Neurodevelopmental Role for L-Type Voltage-Gated Calcium Channels in Neurite Extension and Radial Migration (2018)
  • Author(s): Kamijo Satoshi、Ishii Yuichiro、Horigane Shin-ichiro、Suzuki Kanzo、Ohkura Masamichi、Nakai Junichi、Fujii Hajime、Takemoto-Kimura Sayaka、Bito Haruhiko
  • Journal Title: The Journal of Neuroscience Volume: 38 Issue: 24 Pages: 5551-5566
  • DOI: 10.1523/jneurosci.2357-17.2018
  • Peer Reviewed
• [Presentation] Imaging of multiple Ca2+ signaling components in living neurons and synapses (2018)
  • Author(s): 藤井 哉、井上 昌俊、尾藤 晴彦
  • Organizer: 第41回日本神経科学大会
  • Invited
• [Presentation] Multiplex imaging of neuronal Ca2+-mediated signal transduction (2018)
  • Author(s): Hajime Fujii, Masatoshi Inoue, Haruhiko Bito
  • Organizer: Janelia Conference Fluorescent Proteins and Biological Sensors VI
  • Int'l Joint Research
• [Presentation] Development and imaging of new color indicators for Ca2+ signaling in living neurons (2018)
  • Author(s): Fujii H
  • Organizer: UK-Japan Neuroscience Symposium, Royal Society, London
  • Int'l Joint Research / Invited
• [Presentation] Deciphering Ca2+-dependent signaling pathways underlying cognitive processes. (2018)
  • Author(s): Bito H. Kim R, Inoue M, Inokuchi K, Yokoyama T, Sakai K, Miyazawa Y, Ishii Y, Okamura M, Gammon N, Kobari S, Kondo Y, Sakamoto M, Fujii H.
  • Organizer: China-Japan Joint Symposium "From Neuronal Circuits to Behavior", 95th Annual Meeting of the Physiological Society of Japan
  • Int'l Joint Research
• [Presentation] Novel functions of Ca2+-dependent phosphorylation cascades in the period of neuronal circuit formation. (2017)
  • Author(s): Takemoto-Kimura S, Horigane S, Suzuki K, Kamijo S, Fujii H, Bito H.
  • Organizer: CONBIO2017 Joint Annual Meeting of the Japan Biochemistry Society and the Molecular Biology Society of Japan
• [Presentation] Rational engineering of XCaMPs, a multicolor GECI suite for In vivo imaging of brain circuit dynamics. (2017)
  • Author(s): Inoue M, Takeuchi A, Manita S, Horigane S, Kawakami R, Yamaguchi K, Sakamoto M, Yokoyama H, Kim R, Takemoto-Kimura S, Abe M, Yokoyama T, Quirin S, Ramakrishnan C, Sakimura K, Nemoto T, Kano M, Fujii H, Deisseroth K, Kitamura K, Bito H
  • Organizer: The 48th Annual Meeting of the Society for Neuroscience, Washington Convention Center, Washington DC, USA.
  • Int'l Joint Research
• [Presentation] Development and imaging of new color indicators for Ca2+ signaling in living neurons. (2017)
  • Author(s): Fujii H, Inoue M, Bito H
  • Organizer: The 40th Annual Meeting of the Japan Neuroscience Society, Makuhari, Japan.