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: Granted (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

昨年度から引き続き、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を行った。各プルキンエ細胞での登上線維応答と行動パラメーター（レバー引き、レバー戻し、リッキング、報酬）の関係を線形モデルを用いて解析したところ、半数以上のプルキンエ細胞の登上線維応答は主にレバー引き運動によって説明されることが示された。しかし、驚いたことに、大多数のプルキンエ細胞では、レバー引き運動だけではなく、リッキングや報酬といった異なる情報も登上線維応答に含んでいることが明らかとなった。また、クラスタリングにより反応タイプを分類した結果、同じ反応タイプを示す細胞は空間的に近接していることがわかり、またそれぞれのクラスタはノイズ相関から決定したクラスタと高い割合で一致し、小脳のマイクロゾーン・マイクロコンプレックス仮説を支持した。
小脳の非運動機能について大脳との連関を明らかにするため、遅延報酬の音弁別Go/No-go課題を行っているマウス小脳からの2光子イメージングを行っている。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。
また、研究分担者のHoangらと共同で、カルシウムイメージングデータの精度を向上させるアルゴリズムを開発し、平均で約4倍の時間精度で活動タイミングを推定することが可能となった。

Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

今年度は、レバー引き課題実行中のマウス小脳2光子イメージングのデータ解析が大きく進捗した。現在論文投稿準備中である。研究分担者のHoangと進めていた解析アルゴリズムについて論文を発表した（Hoang et al., Scientific Reports, 2020）また、遅延報酬課題実行中のマウス小脳2光子イメージングについても順調に進んでいる。

Strategy for Future Research Activity

レバー引き運動中の登上線維シグナル解析の論文を発表する。小脳回路の計算機モデルによるレバー引き運動の情報動態解析を領域内の共同研究としてすすめる。遅延課題について訓練を進め、イメージングの実験を行う。

Research Products

• [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] 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