CREB-Arcシグナル活性化による長期記憶制御機構の解明

• Project Area: Principles of memory dynamism elucidated from a diversity of learning systems
• Project/Area Number: 16H01268
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: 尾藤 晴彦 東京大学, 大学院医学系研究科(医学部), 教授 (00291964)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Project Status: Discontinued (Fiscal Year 2017)
• Budget Amount: ¥8,320,000 (Direct Cost: ¥6,400,000、Indirect Cost: ¥1,920,000); Fiscal Year 2017: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
• Keywords: 脳・神経 / 記憶 / CREB

Outline of Annual Research Achievements

本研究では、CREB下流のArc誘導の生理的意義の解明を目的とし、Arc-KOマウスなどを駆使し、in vivo記憶形成における「ポストシナプスNMDA受容体=> Ca2+流入 => CaMK 活性化」=>　CREBリン酸化 => Arc 転写誘導 =>　Arc産物のポストシナプスターゲティング」の機構の貢献について明らかにしようと試みた。平成28年度においては、長期記憶形成時・遠隔記憶想起時に引き起こされるCREB-Arcシグナル時空間的ダイナミクス情報の一端を明らかにし始め、本年度には、記憶形成時・遠隔記憶想起時における興奮性・抑制性神経回路の活動ダイナミクスの操作や同時イメージングを試み始めた。具体的には、CREB-Arc依存的記憶制御がエッセンシャルである時期・部位にて、シナプス活動応答性を強化した人工プロモータE-SAREの機能を活用し、薬剤誘導型DNA リコンビナーゼを発現させるシステムを構築した。これを用い、記憶形成時期の活性化細胞集団の標識と操作が実現した。平成２９年６月３０日付けで平成２９年度新学術領域研究（研究領域提案型）が採択されたため、本研究は廃止された。

Research Progress Status

29年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

29年度が最終年度であるため、記入しない。

Research Products

• [Journal Article] Higher Arc Nucleus-to-Cytoplasm Ratio during Sleep in the Superficial Layers of the Mouse Cortex. (2017)
  • Author(s): Honjoh S, de Vivo L, Okuno H, Bito H, Tononi G, Cirelli C.
  • Journal Title: Front Neural Circuits. Volume: 11 Pages: 60-60
  • DOI: 10.3389/fncir.2017.00060
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Arc restores juvenile plasticity in adult mouse visual cortex. (2017)
  • Author(s): Jenks KR, Kim T, Pastuzyn ED, Okuno H, Taibi AV, Bito H, Bear MF, Shepherd JD.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 114 Pages: 9182-9187
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Histamine H3R receptor activation in the dorsal striatum triggers stereotypies in a mouse model of tic disorders. (2017)
  • Author(s): Rapanelli M, Frick L, Pogorelov V, Ohtsu H, Bito H, Pittenger C.
  • Journal Title: Transl Psychiatry Volume: 7 Issue: 1 Pages: e1013-e1013
  • DOI: 10.1038/tp.2016.290
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Calmodulin kinases: essential regulators in health and disease. (2017)
  • Author(s): Takemoto-Kimura S, Suzuki K, Horigane SI, Kamijo S, Inoue M, Sakamoto M, Fujii H, Bito H.
  • Journal Title: J Neurochem. Volume: - Issue: 6 Pages: 808-818
  • DOI: 10.1111/jnc.14020
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] Specification of a remote memory cell ensemble during cortical tagging through activity-dependent Arc signalling (2017)
  • Author(s): Haruhiko Bito
  • Organizer: The Brain Conferences “Learning, Memory and Synaptic Plasticity”
  • Place of Presentation: Rungstedgaard, Denmark
  • Year and Date: 2017-04-23
  • Int'l Joint Research / Invited
• [Presentation] Deciphering the Role of Arc and Inverse Synaptic Tagging in Long-Term (2017)
  • Author(s): Bito H
  • Organizer: Gordon Research Conference on "Dendrites: Molecules, Structure & Function"
  • Place of Presentation: Renaissance Tuscany Il Ciocco, Lucca (Barga), Italy
  • Year and Date: 2017-03-26
  • Int'l Joint Research / Invited
• [Presentation] Mapping emerging neocortical active ensembles during retrieval of remote memory via functional bioluminescence imaging of Arc promoter activity. (2016)
  • Author(s): Yagishita-Kyo N, Okuno H, Kamijo S, Kawashima T, Uemura Y, Takemoto-Kimura S, Bito H.
  • Organizer: The 46th Annual Meeting of the Society for Neuroscience
  • Place of Presentation: San Diego, California, USA
  • Year and Date: 2016-11-16
  • Int'l Joint Research
• [Presentation] Activity-dependent Arc expression: mechanisms, function and applications. (2016)
  • Author(s): Bito H
  • Organizer: The 19th Korean Society for Brain and Neural Annual Meeting
  • Place of Presentation: KINTEX, Goyang-si, Korea
  • Year and Date: 2016-09-28
  • Int'l Joint Research / Invited
• [Presentation] Labeling, monitoring and manipulating active ensembles. (2016)
  • Author(s): Bito H.
  • Organizer: Conferences Jacques Monod
  • Place of Presentation: Roscoff, France
  • Year and Date: 2016-06-13
  • Int'l Joint Research / Invited