Modular organization of cerebellar cortex during voluntary movements

• Project/Area Number: 17H03543
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurophysiology / General neuroscience
• Research Institution: University of Yamanashi
• Principal Investigator: KITAMURA Kazuo 山梨大学, 大学院総合研究部, 教授 (60423159)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥17,810,000 (Direct Cost: ¥13,700,000、Indirect Cost: ¥4,110,000); Fiscal Year 2019: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2018: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2017: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
• Keywords: 運動制御 / 運動学習 / 2光子イメージング / ２光子イメージング / 登上線維 / 苔状線維 / 薬理遺伝学 / 光遺伝学

Outline of Final Research Achievements

To clarify the physiological significance of the characteristic modular structure of the cerebellar cortex, we performed two-photon calcium imaging and observed climbing fiber activity in the cerebellum of mice performing the go/no-go task. We found that the activity of the climbing fibers represents motor information such as preparation, initiation, and speed of movements, and also found that they represent non-motor information such as go/no-go and rewards signals. In addition, using mice expressing calcium sensors in the mossy fibers of the cerebellum, we could successfully observe their activities during motor behavior.

Academic Significance and Societal Importance of the Research Achievements

脳において最も数多くの神経細胞が存在する小脳は、動物の多様な行動の発現や適応に重要な役割を果たすと考えられている。これまで、小脳の運動制御や運動学習のメカニズムは、単純な反射運動や眼球運動をモデルとして研究されてきたが、外部の環境に応じた判断をして適切な行動を行い報酬を得るといった複雑な行動における小脳の役割についてはよくわかっていない。本研究によって、行動に関する様々な情報が各モジュールで並列に処理されていることを示した。この結果は、これまで主に運動機能に着目して研究が進められてきた小脳が、非運動機能に関わる情報も同時に処理し、高度な行動の発現に貢献していることを示している。

Research Products

• [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] 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] 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] 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] 小脳の運動機能と非運動機能：マウスを用いた研究． (2019)
  • Author(s): 喜多村和郎
  • Organizer: 第9回小脳研究会
• [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] 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