Modular organization of cerebellar climbing fiber inputs during goal-directed behavior

  1. Shinichiro Tsutsumi  Is a corresponding author
  2. Naoki Hidaka
  3. Yoshikazu Isomura
  4. Masanori Matsuzaki
  5. Kenji Sakimura
  6. Masanobu Kano  Is a corresponding author
  7. Kazuo Kitamura  Is a corresponding author
  1. The University of Tokyo, Japan
  2. Tamagawa University, Japan
  3. Niigata University, Japan
  4. University of Yamanashi, Japan

Abstract

The cerebellum has a parasagittal modular architecture characterized by precisely organized climbing fiber (CF) projections congruent with alternating aldolase C/zebrin II expression. However, behavioral relevance of CF inputs to individual modules remains poorly understood. Here, we used two-photon calcium imaging in the cerebellar hemisphere Crus II in mice performing an auditory go/no-go task to investigate the functional differences in CF inputs to modules. CF signals in medial modules show anticipatory decreases, early increases, secondary increases, and reward-related increases or decreases, which represent quick motor initiation, go cues, fast motor behavior, and positive reward outcomes. CF signals in lateral modules show early increases and reward-related decreases, which represent no-go and/or go cues and positive reward outcomes. The boundaries of CF functions broadly correspond to those of aldolase C patterning. These results indicate that spatially segregated CF inputs in different modules play distinct roles for execution of goal-directed behavior.

Data availability

Data analysed for all the figures are included in the manuscript and source data files. The Aldoc-tdTomato mouse line will be available at RIKEN Bio Resource Center.

Article and author information

Author details

  1. Shinichiro Tsutsumi

    Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
    For correspondence
    stsutsumi@m.u-tokyo.ac.jp
    Competing interests
    The authors declare that no competing interests exist.
  2. Naoki Hidaka

    Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  3. Yoshikazu Isomura

    Brain Science Institute, Tamagawa University, Tokyo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  4. Masanori Matsuzaki

    Department of Cellular and Molecular Physiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3872-4322
  5. Kenji Sakimura

    Department of Cellular Neurobiology, Brain Research Institute, Niigata University, Niigata, Japan
    Competing interests
    The authors declare that no competing interests exist.
  6. Masanobu Kano

    Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
    For correspondence
    mkano-tky@m.u-tokyo.ac.jp
    Competing interests
    The authors declare that no competing interests exist.
  7. Kazuo Kitamura

    Department of Neurophysiology, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan
    For correspondence
    kitamurak@yamanashi.ac.jp
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8956-4122

Funding

Japan Society for the Promotion of Science (23115504)

  • Kazuo Kitamura

Japan Society for the Promotion of Science (25115705)

  • Kazuo Kitamura

Japan Society for the Promotion of Science (25290003)

  • Kazuo Kitamura

Japan Society for the Promotion of Science (15H01426)

  • Kazuo Kitamura

Japan Society for the Promotion of Science (17H03543)

  • Kazuo Kitamura

Japan Society for the Promotion of Science (17H06313)

  • Kazuo Kitamura

Japan Society for the Promotion of Science (21220006)

  • Masanobu Kano

Japan Society for the Promotion of Science (25000015)

  • Masanobu Kano

Japan Society for the Promotion of Science (18H04012)

  • Masanobu Kano

Ministry of Education, Culture, Sports, Science, and Technology (Comprehensive Brain Science Network)

  • Kenji Sakimura
  • Masanobu Kano
  • Kazuo Kitamura

Ministry of Education, Culture, Sports, Science, and Technology (Brain Information Dynamics)

  • Kazuo Kitamura

Ministry of Education, Culture, Sports, Science, and Technology (The Strategic Research Programme for Brain Sciences)

  • Masanobu Kano

Japan Agency for Medical Research and Development (Brain/MINDS)

  • Masanobu Kano
  • Kazuo Kitamura

Takeda Science Foundation

  • Kazuo Kitamura

Uehara Memorial Foundation

  • Kazuo Kitamura

Japan Society for the Promotion of Science (25560432)

  • Kazuo Kitamura

Japan Society for the Promotion of Science (25113705)

  • Kazuo Kitamura

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All experiments were approved by the Animal Experiment Committees of the University of Tokyo (#P08-015) and University of Yamanashi (#A27-1).

Reviewing Editor

  1. Megan R Carey, Champalimaud Foundation, Portugal

Publication history

  1. Received: March 20, 2019
  2. Accepted: October 7, 2019
  3. Accepted Manuscript published: October 9, 2019 (version 1)
  4. Version of Record published: November 11, 2019 (version 2)

Copyright

© 2019, Tsutsumi et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Shinichiro Tsutsumi
  2. Naoki Hidaka
  3. Yoshikazu Isomura
  4. Masanori Matsuzaki
  5. Kenji Sakimura
  6. Masanobu Kano
  7. Kazuo Kitamura
(2019)
Modular organization of cerebellar climbing fiber inputs during goal-directed behavior
eLife 8:e47021.
https://doi.org/10.7554/eLife.47021
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