Optical Measurement and Control of Multiareal Brain Information Dynamics in Cognition and Movement

• 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: KITAMURA Kazuo 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 / 運動 / 学習 / 2光子イメージング / ２光子イメージング / 高次機能

Outline of Final Research Achievements

The cerebrum and cerebellum communicate each other to achieve sophisticated motor control and motor learning. The cerebro-cerebeller loop also plays an important role in higher-order functions. To elucidate neural circuit mechanisms for these functions, we used two-photon imaging to observe neural activity in mice performing cognitive-motor tasks, and revealed the neural representations regarding sensation, movement, and reward. We also developed novel calcium sensors that can measure neural activity with unprecedented accuracy and a data analysis method.

Academic Significance and Societal Importance of the Research Achievements

小脳は運動に関わる脳領域として長年研究が進められてきたが、その詳細な神経回路メカニズムについては未だ不明な点が多い。さらに、最近では報酬や判断など運動とは直接関係ない情報が小脳にも伝えられていることが明らかとなって注目を集めている。本研究では、これらの情報表現がどのようなものかを認知運動課題を実行中のマウスにおいて明らかにした。素早く正確な運動や判断を実現するための脳メカニズムとその獲得原理の解明に貢献する。

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 Issue: 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 Issue: 9 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 Issue: 1 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 Issue: 12 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: Scientific Reports Volume: 9 Issue: 1 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 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 Issue: 5 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 Rep. Volume: 22 Issue: 1 Pages: 123-135
  • DOI: 10.1016/j.celrep.2017.12.012
  • Peer Reviewed / Open Access
• [Journal Article] Maturation of Cerebellar Purkinje Cell Population Activity during Postnatal Refinement 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