1. Neuroscience
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TRPC3 is a major contributor to functional heterogeneity of cerebellar Purkinje cells

  1. Bin Wu
  2. François G C Blot
  3. Aaron Benson Wong
  4. Catarina Osório
  5. Youri Adolfs
  6. R Jeroen Pasterkamp
  7. Jana Hartmann
  8. Esther B E Becker
  9. Henk-Jan Boele
  10. Chris I De Zeeuw
  11. Martijn Schonewille  Is a corresponding author
  1. Erasmus Medical Center, Netherlands
  2. University Medical Center Utrecht, Netherlands
  3. Technische Universität München, Germany
  4. University of Oxford, United Kingdom
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Cite this article as: eLife 2019;8:e45590 doi: 10.7554/eLife.45590

Abstract

Despite the canonical homogeneous character of its organization, the cerebellum plays differential computational roles in distinct sensorimotor behaviors. Previously we showed that Purkinje cell activity differs between zebrin-negative (Z-) and zebrin-positive (Z+) modules (Zhou et al., 2014). Here, using gain-of-function and loss-of-function mouse models, we show that transient receptor potential cation channel C3 (TRPC3) controls the simple spike activity of Z-, but not Z+ Purkinje cells. In addition, TRPC3 regulates complex spike rate and their interaction with simple spikes, exclusively in Z- Purkinje cells. At the behavioral level, TRPC3 loss-of-function mice show impaired eyeblink conditioning, which is related to Z- modules, whereas compensatory eye movement adaptation, linked to Z+ modules, is intact. Together, our results indicate that TRPC3 is a major contributor to the cellular heterogeneity that introduces distinct physiological properties in Purkinje cells, conjuring functional heterogeneity in cerebellar sensorimotor integration.

Article and author information

Author details

  1. Bin Wu

    Department of Neuroscience, Erasmus Medical Center, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4198-1661
  2. François G C Blot

    Department of Neuroscience, Erasmus Medical Center, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  3. Aaron Benson Wong

    Department of Neuroscience, Erasmus Medical Center, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1650-2710
  4. Catarina Osório

    Department of Neuroscience, Erasmus Medical Center, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  5. Youri Adolfs

    Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  6. R Jeroen Pasterkamp

    Department of Translational Neuroscience, University Medical Center Utrecht, Utrecht, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1631-6440
  7. Jana Hartmann

    Institute of Neuroscience, Technische Universität München, Munich, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Esther B E Becker

    Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5238-4902
  9. Henk-Jan Boele

    Department of Neuroscience, Erasmus Medical Center, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  10. Chris I De Zeeuw

    Department of Neuroscience, Erasmus Medical Center, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5628-8187
  11. Martijn Schonewille

    Department of Neuroscience, Erasmus Medical Center, Rotterdam, Netherlands
    For correspondence
    m.schonewille@erasmusmc.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2675-1393

Funding

European Commission (ERC-Stg #680235)

  • Martijn Schonewille

China Scholarship Council (#201306230130)

  • Bin Wu

Nederlandse Organisatie voor Wetenschappelijk Onderzoek (ALW / Zon-Mw)

  • Chris I De Zeeuw

European Commission (ERC-Adv)

  • Chris I De Zeeuw

European Commission (ERC-POC)

  • Chris I De Zeeuw

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

Ethics

Animal experimentation: This study was performed under and all of the animals were handled according to a project license approved by the Dutch Central Committee for Animal Experiments (CCD, AVD #101002015273). Each experiment was separately verified and approved by the Animal Welfare Body (IvD/AWB, various numbers). All surgery was performed under isoflurane anesthesia combined with local anesthetics and analgesics in an effort to minimize suffering.

Reviewing Editor

  1. Jennifer L Raymond, Stanford School of Medicine, United States

Publication history

  1. Received: February 8, 2019
  2. Accepted: August 18, 2019
  3. Accepted Manuscript published: September 5, 2019 (version 1)
  4. Version of Record published: September 9, 2019 (version 2)

Copyright

© 2019, Wu 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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