記憶・情動における多領野間脳情報動態の光学的計測と制御

2018 Fiscal Year Annual Research Report

• Project Area: Brain information dynamics underlying multi-area interconnectivity and parallel processing
• Project/Area Number: 17H06312
• 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): 2017-06-30 – 2022-03-31
• Keywords: 神経科学 / 脳・神経

Outline of Annual Research Achievements

長期記憶の情報表現は記憶の古さにより遷移し、さらに領野間で転送される。ではなぜ過去の記憶を他の記憶と混在させず、正確に想起することが可能なのか。この疑問を解明するため、本年度は、以下の項目に焦点を合わせ、研究を進めた。１）活性化細胞集団と記憶痕跡を多領野で同時に標識するため、ウィルスベクターと組み合わせて記憶痕跡標識操作を実現する遺伝子改変マウスを前年度に作出した。これを用いて、恐怖条件付け記憶課題において、近時記憶の想起中には活動していないが、遠隔記憶の想起に必要十分な記憶痕跡の性質を持ちうる前頭皮質細胞の存在を明らかにし、さらにこのような記憶痕跡の成熟過程を制御する分子シグナルの存在も解明した。２）当研究室で開発した新規カルシウムインディケーターXCaMPを用いて、新規物体認知遂行時における前頭皮質の異なる３細胞種（CaMKII陽性興奮性＋Parvalbumin陽性抑制性＋Somatostatin陽性抑制性）アンサンブルの同時活動記録記憶を世界に先駆けて実現した。３）恐怖情動の近似記憶・遠隔記憶制御における多領野間連関を司る脳部位の光遺伝学的活性化技術を樹立し、想起を引き起こすエングラム細胞同定と長期記憶安定化を引き起こすエングラム操作を実現した。
次年度以降、これらの手法を組み合わせ、多領野間の記憶構造ループの再編・安定化機構を、生きたマウス脳で再現し解明していく予定である。

Current Status of Research Progress

1: Research has progressed more than it was originally planned.

Reason

恐怖情動の長期記憶を司る多領野間記憶構造ループの解明を実現していくためのマイルストーンである技術開発（１．活性細胞集団の自在な標識と操作、２．多数の活性化アンサンブルの同時記録、３．多部位における記憶痕跡の自在な光遺伝学的活性化）を達成する目途が立ったため。

Strategy for Future Research Activity

計画に基づき、先年度の成果を活用する研究を推進するとともに、総括班研究と連動し、他の計画班員や公募班員として連携・共
同研究を推進していく。

Research Products

• [Int'l Joint Research] Stanford University(米国)
  • Country Name: U.S.A.
  • Counterpart Institution: Stanford University
• [Int'l Joint Research] Cornell University/Stanford University(米国)
  • Country Name: U.S.A.
  • Counterpart Institution: Cornell University/Stanford University
• [Int'l Joint Research] MIT(米国)
  • Country Name: U.S.A.
  • Counterpart Institution: MIT
• [Int'l Joint Research] Stanford University(米国)
  • Country Name: U.S.A.
  • Counterpart Institution: Stanford University
• [Journal Article] Sustained rescue of prefrontal circuit dysfunction by antidepressant-induced spine formation. (2019)
  • Author(s): Moda-Sava RN, Murdock MH, Parekh PK, Fetcho RN, Huang BS, Huynh TN, Witztum J, Shaver DC, Rosenthal DL, Alway EJ, Lopez K, Meng Y, Nellissen L, Grosenick L, Milner TA, Deisseroth K, Bito H, Kasai H, Liston C.
  • Journal Title: Science Volume: 364 Pages: eaat8078
  • DOI: 10.1126/science.aat8078
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Rational engineering of XCaMPs, a multicolor GECI suite for in vivo imaging of complex brain circuit dynamics. (2019)
  • Author(s): Inoue M, Takeuchi A, Manita S, Horigane S-i, Sakamoto M, Kawakami R, Yamaguchi K, Otomo K, Yokoyama H, Kim R, Yokoyama T, Takemoto-Kimura S, Abe M, Okamura M, Kondo Y, Quirin S, Ramakrishnan C, Imamura T, Sakimura K, Nemoto T, Kano M, Fujii H, Deisseroth K, Kitamura K, Bito H.
  • Journal Title: Cell Volume: 177 Pages: 印刷中
  • DOI: 10.1016/j.cell.2019.04.007
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Involvement of SRF coactivator MKL2 in BDNF-mediated activation of the synaptic activity-responsive element in the Arc gene. (2019)
  • Author(s): Kikuchi K, Ihara D, Fukuchi M, Tanabe H, Ishibashi Y, Tsujii J, Tsuda M, Kaneda M, Sakagami H, Okuno H, Bito H, Yamazaki Y, Ishikawa M, Tabuchi A.
  • Journal Title: Journal of Neurochemistry Volume: 148 Pages: 204-218
  • DOI: 10.1111/jnc.14596
  • Peer Reviewed
• [Journal Article] Long-term consolidation of ensemble neural plasticity patterns in hippocampal area CA1. (2018)
  • Author(s): Attardo A, Lu J, Kawashima T, Okuno H, Fitzgerald JE, Bito H, Schnitzer MJ.
  • Journal Title: Cell Reports Volume: 25 Pages: 640-650
  • DOI: 10.1016/j.celrep.2018.09.064
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Astrocytes in the mouse visual cortex reliably respond to visual stimulation. (2018)
  • Author(s): Sonoda K, Matsui T, Bito H, Ohki K.
  • Journal Title: Biochem Biophys Res Commun. Volume: 505 Pages: 1216-1222
  • DOI: 10.1016/j.bbrc.2018.10.027
  • Peer Reviewed
• [Journal Article] Locally coordinated synaptic plasticity of visual cortex neurons in vivo. (2018)
  • Author(s): El-Boustani S, Ip JPK, Breton-Provencher V, Knott GW, Okuno H, Bito H, Sur M.
  • Journal Title: Science Volume: 360 Pages: 1349-1354
  • DOI: 10.1126/science.aao0862
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] A Critical Neurodevelopmental role for L-type voltage-gated calcium channels in neurite extension and radial migration. (2018)
  • Author(s): Kamijo S, Ishii Y, Horigane SI, Suzuki K, Ohkura M, Nakai J, Fujii H, Takemoto-Kimura S, Bito H.
  • Journal Title: Journal of Neuroscience Volume: 38 Pages: 5551-5566
  • DOI: 10.1523/JNEUROSCI.2357-17.2018
  • Peer Reviewed
• [Journal Article] CaMKIIβ is localized in dendritic spines as both drebrin-dependent and drebrin-independent pools. (2018)
  • Author(s): Yamazaki H, Sasagawa Y, Yamamoto H, Bito H, Shirao T.
  • Journal Title: Journal of Neurochemistry Volume: 146 Pages: 145-159
  • DOI: 10.1111/jnc.14449
  • Peer Reviewed
• [Presentation] Inverse synaptic tagging: an inactive synapse-targeted mechanism to capture activity-induced Arc (2019)
  • Author(s): Haruhiko Bito, Yuichiro Ishii, Hiroyuki Okuno
  • Organizer: 9th FAOPS Congress
  • Int'l Joint Research / Invited
• [Presentation] Arc-dependent long-term memory control (2018)
  • Author(s): Bito H
  • Organizer: 13th International Conference of Neurons and Brain Diseases
  • Int'l Joint Research / Invited
• [Presentation] Ca2+-dependent signaling in regulation of cognitive behavior (2018)
  • Author(s): Bito H
  • Organizer: 41st Annual Meeting of the Japan Neuroscience Society
  • Invited
• [Presentation] Probing Ca2+ and Ca2+-dependent gene expression in vivo to decipher information processing underlying cognitive behavior. (2018)
  • Author(s): Inoue M, Yokoyama T, Fujii H, Sakamoto M, Bito H.
  • Organizer: Janelia Conference Fluorescent Proteins and Biological Sensors VI
  • Int'l Joint Research / 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] Specification of a remote memory cell ensemble during cortical tagging. (2018)
  • Author(s): Ryang Kim, Yayoi Kondo, Takashi Kawashima, Michiko Okamura, Masatoshi Inoue, Yuichiro Ishii, Kasumi Inokuchi, Kazuki Sakai, Mio Nonaka, Masayuki Sakamoto, Hiroyuki Okuno, Haruhiko Bito.
  • Organizer: Annual Meeting of the Society for Neuroscience 2018
  • Int'l Joint Research
• [Presentation] Specification of a remote memory cell ensemble during cortical tagging. (2018)
  • Author(s): Ryang Kim, Yayoi Kondo, Takashi Kawashima, Michiko Okamura, Masatoshi Inoue, Yuichiro Ishii, Kasumi Inokuchi, Kazuki Sakai, Mio Nonaka, Masayuki Sakamoto, Hiroyuki Okuno, Haruhiko Bito.
  • Organizer: The 17th Annual Molecular Cellular Cognition Society Symposium.
  • Int'l Joint Research / Invited
• [Presentation] Multiplex imaging of neural activity and signaling dynamics. (2018)
  • Author(s): Bito H
  • Organizer: Cold Spring Harbor Asia Meeting Announcement: Advances in Optical Imaging of Living Cells & Organisms: Focus on the Brain
  • Int'l Joint Research / Invited
• [Presentation] Ultrafast two-photon microscopy for high-speed brain imaging in awake mice. (2018)
  • Author(s): Radoslaw Chrapkiewicz, Tong Zhang, Oscar Hernandez, Adam S. Shai, Mark J. Wagner, Yanping Zhang, Cheng-Hsun Wu, Jin Zhong Li, Yiyang Gong, Masatoshi Inoue, Haruhiko Bito, Mark J. Schnitzer.
  • Organizer: SPIE Photonics Europe
  • Int'l Joint Research
• [Funded Workshop] Cold Spring Harbor Asia Meeting Announcement: Advances in Optical Imaging of Living Cells & Organisms: Focus on the Brain (2018)