認知・運動における多領野間脳情報動態の光学的計測と制御

• Project Area: Brain information dynamics underlying multi-area interconnectivity and parallel processing
• Project/Area Number: 17H06313
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Complex systems
• Research Institution: University of Yamanashi
• Principal Investigator: 喜多村 和郎 山梨大学, 大学院総合研究部, 教授 (60423159)
• Co-Investigator(Kenkyū-buntansha): 徳田 功 立命館大学, 理工学部, 教授 (00261389) ; 山崎 美和子 北海道大学, 医学研究院, 准教授 (10431305) ; HOANG・THIEN HUU 株式会社国際電気通信基礎技術研究所, 脳情報通信総合研究所, 研究員 (50772307)
• Project Period (FY): 2017-06-30 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥151,320,000 (Direct Cost: ¥116,400,000、Indirect Cost: ¥34,920,000); Fiscal Year 2021: ¥27,170,000 (Direct Cost: ¥20,900,000、Indirect Cost: ¥6,270,000); Fiscal Year 2020: ¥27,170,000 (Direct Cost: ¥20,900,000、Indirect Cost: ¥6,270,000); Fiscal Year 2019: ¥27,170,000 (Direct Cost: ¥20,900,000、Indirect Cost: ¥6,270,000); Fiscal Year 2018: ¥33,410,000 (Direct Cost: ¥25,700,000、Indirect Cost: ¥7,710,000); Fiscal Year 2017: ¥36,400,000 (Direct Cost: ¥28,000,000、Indirect Cost: ¥8,400,000)
• Keywords: 神経科学 / 大脳小脳 / 2光子イメージング / ２光子イメージング / 運動 / 高次機能

Outline of Annual Research Achievements

本研究課題の最終目標の一つである、認知運動学習における小脳の役割、特に、教師あり学習に必要な誤差信号の存在や分布を調べるために、これまで開発してきた音弁別Lick/No-lick課題をもとに改良したマウス適応行動課題を開発した。運動の目標位置や提示時間を変化させることで運動に誤差を生じさせ、それに基づいてマウスが適応的に運動を修正する過程を評価する。運動の目標位置を変化させる課題では、よく用いられるサッケード適応課題などと同様に、目標位置変化に対してマウスが予測的に運動を変化させる過程が観察され、誤差とそれに基づく運動適応を正しく評価できると期待された。さらに、報酬および報酬予測誤差シグナルの小脳における役割を明らかにするための課題を開発した。この課題においても、報酬の提示・不提示に応じてマウスが適応的に行動を変化させていく過程を捉えることが可能であることを確認した。開発した課題を実行中のマウス小脳において誤差を伝える登上線維シグナルを2光子カルシウムイメージングにより解析している。小脳の機能モジュールであるゾーン構造ごとの機能を調べるため、これらの実験は、ゾーンを可視化できるAldoc-tdTomatoマウスを用いて行った。
レバー引き課題実行中のマウス小脳2光子イメージングによる登上線維シグナルの解析について、追加の解析および論文の修正を行った。
研究分担者のHoang、研究協力者の川人、外山らと共同で、Go/No-go課題を学習中のマウス小脳における登上線維シグナルの解析を進めた。小脳ゾーンごとに運動開始のタイミング制御やNo-go学習に対応するシグナルが観察され、これまでの小脳制御学習理論に一致するシグナルが観察された。

Research Progress Status

令和3年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

令和3年度が最終年度であるため、記入しない。

Research Products

• [Int'l Joint Research] University of Zurich(スイス)
• [Journal Article] A Flp-dependent G-CaMP9a transgenic mouse for neuronal imaging in?vivo (2022)
  • Author(s): Sakamoto Masayuki, Inoue Masatoshi, Takeuchi Atsuya, Kobari Shigetaka, Yokoyama Tatsushi, Horigane Shin-ichiro, Takemoto-Kimura Sayaka, Abe Manabu, Sakimura Kenji, Kano Masanobu, Kitamura Kazuo, Fujii Hajime, Bito Haruhiko
  • Journal Title: Cell Reports Methods Volume: 2 Pages: 100168-100168
  • DOI: 10.1016/j.crmeth.2022.100168
  • Peer Reviewed / Open Access
• [Journal Article] A database and deep learning toolbox for noise-optimized, generalized spike inference from calcium imaging (2021)
  • Author(s): Rupprecht Peter, Carta Stefano, Hoffmann Adrian, Echizen Mayumi, Blot Antonin, Kwan Alex C., Dan Yang, Hofer Sonja B., Kitamura Kazuo, Helmchen Fritjof, Friedrich Rainer W.
  • Journal Title: Nature Neuroscience Volume: 24 Pages: 1324-1337
  • DOI: 10.1038/s41593-021-00895-5
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Improved hyperacuity estimation of spike timing from calcium imaging (2020)
  • Author(s): Hoang Huu、Sato Masa-aki、Shinomoto Shigeru、Tsutsumi Shinichiro、Hashizume Miki、Ishikawa Tomoe、Kano Masanobu、Ikegaya Yuji、Kitamura Kazuo、Kawato Mitsuo、Toyama Keisuke
  • Journal Title: Scientific Reports Volume: 10 Pages: 17844-17844
  • DOI: 10.1038/s41598-020-74672-y
  • Peer Reviewed / Open Access
• [Journal Article] Activation of the reward system ameliorates passive cutaneous anaphylactic reaction in mice (2020)
  • Author(s): Nakajima Shotaro、Manita Satoshi、Yu Guannan、Ishimaru Kayoko、Kono Koji、Kitamura Kazuo、Nakao Atsuhito
  • Journal Title: Allergy Volume: 75 Pages: 3275-3279
  • DOI: 10.1111/all.14442
  • Peer Reviewed / Open Access
• [Journal Article] Modular organization of cerebellar climbing fiber inputs during goal-directed behavior. (2019)
  • Author(s): Tsutsumi S, Hidaka N, Isomura Y, Matsuzaki M, Sakimura K, Kano M, Kitamura K.
  • Journal Title: eLife Volume: 8
  • DOI: 10.7554/elife.47021
  • Peer Reviewed / Open Access
• [Journal Article] mGluR1 in cerebellar Purkinje cells is essential for the formation but not expression of associative eyeblink memory (2019)
  • Author(s): Nakao Harumi、Kishimoto Yasushi、Hashimoto Kouichi、Kitamura Kazuo、Yamasaki Miwako、Nakao Kazuki、Watanabe Masahiko、Kano Masanobu、Kirino Yutaka、Aiba Atsu
  • Journal Title: Sci Rep. Volume: 9 Pages: 7353-7353
  • DOI: 10.1038/s41598-019-43744-z
  • Peer Reviewed / Open Access
• [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 SI, 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: 1346-1360
  • DOI: 10.1016/j.cell.2019.04.007
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Patchwork-type spontaneous activity in neonatal barrel cortex layer 4 transmitted via thalamocortical projections. (2018)
  • Author(s): Mizuno, H., Ikezoe, K., Nakazawa, S., Sato, T., Kitamura, K., Iwasato, T.
  • Journal Title: Cell reports Volume: 22 Pages: 123-135
  • DOI: 10.1016/j.celrep.2017.12.012
  • Peer Reviewed / Open Access
• [Journal Article] Maturation of cercbellar purkinje cell population activity during postnatal refinemcnt of climbing fiber network. (2017)
  • Author(s): Good JM, Mahoney M, Miyazaki T, Tanaka KF, Sakimura K, Watanabe M, Kitamura K, Kano M.
  • Journal Title: Cell Rep Volume: 21(8) Issue: 8 Pages: 2066-2073
  • DOI: 10.1016/j.celrep.2017.10.101
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Neural substrates for deciding timing of self-initiated locomotion (2022)
  • Author(s): Masayoshi Murakami, Fanny Cazettes, Zachary F. Mainen, Kazuo Kitamura
  • Organizer: The 99th Annual Meeting of the Physiological Society of Japan
  • Int'l Joint Research
• [Presentation] Synchronicity changes of complex spike activities in cerebellar Purkinje cells during auditory go/no-go task learning studied by hyperacuity two-photon recordings (2021)
  • Author(s): Huu Thien Hoang, Shinichiro Tsutsumi, Kazuo Kitamura, Mitsuo Kawato, Keisuke Toyama
  • Organizer: The 44th Annual Meeting of the Japan Neuroscience Society/The 1st CJK International Meeting
  • Int'l Joint Research
• [Presentation] A novel reaching and grasping task for head-fixed mice with an automated agar cube dispenser (2021)
  • Author(s): Satoshi Manita, Koji Ikezoe, Kazuo Kitamura
  • Organizer: The 44th Annual Meeting of the Japan Neuroscience Society/The 1st CJK International Meeting
  • Int'l Joint Research
• [Presentation] Encoding model analysis of complex spikes of Purkinje cells in mice cerebellum during a voluntary lever-pull task (2021)
  • Author(s): Koji Ikezoe, Naoki Hidaka, Satoshi Manita, Masayoshi Murakami, Shinichiro Tsutsumi, Yoshikazu Isomura, Masanobu Kano, Kazuo Kitamura
  • Organizer: The 44th Annual Meeting of the Japan Neuroscience Society/The 1st CJK International Meeting
  • Int'l Joint Research
• [Presentation] 1.Calibrated spike inference from calcium imaging data: generalization across datasets, imaging rates and noise levels (2020)
  • Author(s): Rupprecht P, Carta S, Echizen M, Hoffmann A, Kitamura K, Friedrich RW, Helmchen F
  • Organizer: FENS virtual forum
  • Int'l Joint Research
• [Presentation] 1.Cerebellar climbing fiber signals represent voluntary forelimb lever-pull trajectories. (2019)
  • Author(s): Hidaka N, Ikezoe K, Tsutsumi S, Isomura Y, Kano M, Kitamura K
  • Organizer: Neuro2019
  • Int'l Joint Research
• [Presentation] 2.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, (12名省略), Kitamura K, Bito H
  • Organizer: Neuro2019
  • Int'l Joint Research
• [Presentation] 3.Neuronal representation for speed and acceleration of walking in mouse cerebellar cortex. (2019)
  • Author(s): Ikezoe K, Kitamura K
  • Organizer: Neuro2019
  • Int'l Joint Research
• [Presentation] Functional connectivity between the neocortex and the cerebellum. (2019)
  • Author(s): Kitamura K
  • Organizer: IBRO2019
  • Int'l Joint Research
• [Presentation] Measurement of multiple cerebellar mossy fiber activities by calcium imaging in mouse. (2019)
  • Author(s): Manita S, Ikezoe K, Sato M, Ohkura M, Nakai J, Hayashi Y, Kitamura K.
  • Organizer: 9th FAOPS
  • Int'l Joint Research
• [Presentation] Neural substrates of action timing decisions. (2019)
  • Author(s): Murakami M, Cazettes F, Mainen ZF, Kitamura K.
  • Organizer: 9th FAOPS
  • Int'l Joint Research
• [Presentation] Neuronal tuning to speed and acceleration of locomotion in mouse cerebellar cortex. (2019)
  • Author(s): Ikezoe K, Kitamura K.
  • Organizer: 9th FAOPS
  • Int'l Joint Research
• [Presentation] Patchwork-type spontaneous activity in neonatal somatosensory cortex transmitted via thalamocortical projections. (2018)
  • Author(s): Mizuno H, Ikezoe K, Nakazawa S, Sato T, Kitamura K, Iwasato T.
  • Organizer: Neuroscience 2018
  • Int'l Joint Research
• [Presentation] Control of micturition by manipulation of the activity of the anterior cingulate cortex. (2018)
  • Author(s): Mochizuki T, Manita S, Shimura H, Imai Y, Ihara T, Kira S, Nakagomi H, Sawada N, Mitsui T, Takeda M, Kitamura K.
  • Organizer: Neuroscience 2018
  • Int'l Joint Research
• [Presentation] Activity of cerebellar climbing fibers represents forelimb movements during voluntary lever-pull task in mice. (2018)
  • Author(s): Hidaka N, Tsutsumi S, Ikezoe K, Isomura Y, Kano M, Kitamura K.
  • Organizer: Neuroscience 2018
  • Int'l Joint Research
• [Presentation] Organization of the functional inputs from the sensorimotor cortex to the cerebellum revealed by transcranial optogenetic mapping. (2018)
  • Author(s): Choo M, Hira R, Matsuzaki M, Ikezoe K, Augustine GJ, Kano M, Kitamura K.
  • Organizer: Neuroscience 2018
  • Int'l Joint Research
• [Presentation] Regulation of micturition by the activity of the anterior cingulate cortex in mice. (2018)
  • Author(s): Mochizuki T, Manita S, Mitsui T, Takeda M, Kitamura K.
  • Organizer: Neuroscience 2018
  • Int'l Joint Research
• [Presentation] 小脳の運動機能と非運動機能：マウスを用いた研究． (2018)
  • Author(s): 喜多村和郎
  • Organizer: 第9回小脳研究会
• [Presentation] A novel method for assessment of reaching and grasping movements in head-fixed mice (2018)
  • Author(s): Satoshi Manita, Koji Ikezoe, Kazuo Kitamura
  • Organizer: 第９４回日本生理学大会
• [Presentation] 随意運動における小脳登上線維シグナルの2光子イメージング解析 (2017)
  • Author(s): 日高直樹，堤新一郎, 池添貢司, 礒村宣和, 狩野方伸, 喜多村和郎
  • Organizer: 第64回中部日本生理学会
• [Presentation] Functions of cerebellar modules during goal-directed behavior (2017)
  • Author(s): Kazuo Kitamura, Shinichiro Tsutsumi, Naoki Hidaka, Yoshikazu Isomura, Masanori Matsuzaki, Kenji Sakimura, Masanobu Kano
  • Organizer: Neuroscience2017
  • Int'l Joint Research
• [Presentation] Maturation of cerebellar climbing fiber and Purkinje cell population activities during postnatal development (2017)
  • Author(s): Michael Mahoney, Jean-Marc Good, Taisuke Miyazaki, Kenji F Tanaka, Kenji Sakimura, Masahiko Watanabe, Kazuo Kitamura, Masanobu Kano
  • Organizer: Neuroscience2017
  • Int'l Joint Research
• [Presentation] Barrel-confined patchwork activity of the somatosensory layer 4 neurons in neonates (2017)
  • Author(s): Hidenobu Mizuno, Koji Ikezoe, Takuya Sato, Kazuo Kitamura, Takuji Iwasato
  • Organizer: Neuroscience2017
  • Int'l Joint Research
• [Presentation] Establishment of a method to observe cerebellar activities during reaching and grasping in mice (2017)
  • Author(s): Satoshi Manita, Koji Ikezoe, Taiyo Kawaguchi, Kazuo Kitamura
  • Organizer: Neuroscience2017
  • Int'l Joint Research
• [Presentation] Two-photon imaging of cerebellar climbing fiber signals during a voluntary movement (2017)
  • Author(s): Naoki Hidaka, Shinichiro Tsutsumi, Koji Ikezoe, Yoshikazu Isomura, Masanobu Kano, Kazuo Kitamura
  • Organizer: Neuroscience2017
  • Int'l Joint Research
• [Presentation] 小脳モジュールの機能解析 (2017)
  • Author(s): 喜多村和郎
  • Organizer: 次世代脳冬のシンポジウム
• [Presentation] ２光子イメージングによる随意運動中のマウスの小脳登上線維シグナル解析 (2017)
  • Author(s): 日高直樹，堤新一郎, 池添貢司, 礒村宣和, 狩野方伸, 喜多村和郎
  • Organizer: 次世代脳冬のシンポジウム
• [Presentation] Two-photon imaging of cerebellar activity in vivo (2017)
  • Author(s): Kazuo Kitamura
  • Organizer: Two-photon functional imaging in the living brain: Theory and Practice
  • Invited