Differential spatiotemporal development of Purkinje cell populations and cerebellum-dependent sensorimotor behaviors

Abstract

Distinct populations of Purkinje cells (PCs) with unique molecular and connectivity features are at the core of the modular organization of the cerebellum. Previously, we showed that firing activity of Purkinje cells differs between ZebrinII-positive (Z+) and -negative (Z−) cerebellar modules (Zhou et al., 2014; Wu et al., 2019). Here, we investigate the timing and extent of PC differentiation during development in mice. We found that several features of PCs, including activity levels, dendritic arborisation, axonal shape and climbing fiber input, develop differentially between nodular and anterior PC populations. Although all PCs show a particularly rapid development in the second postnatal week, anterior PCs typically have a prolonged physiological and dendritic maturation. In line herewith, younger mice exhibit attenuated anterior-dependent eyeblink conditioning, but faster nodular-dependent compensatory eye movement adaptation. Our results indicate that specific cerebellar regions have unique developmental timelines which match with their related, specific forms of cerebellum-dependent behaviors.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Gerrit Cornelis Beekhof

    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:" 0000-0002-3038-5023
  2. Catarina Osório

    Department of Neuroscience, King's College London, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5228-0599
  3. Joshua J White

    Pathology and Immunology, Neuroscience, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Scott van Zoomeren

    Department of Neuroscience, Erasmus Medical Center, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  5. Hannah van der Stok

    Department of Neuroscience, Erasmus Medical Center, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  6. Bilian Xiong

    Department of Neuroscience, Erasmus Medical Center, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  7. Ingo HMS Nettersheim

    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:" 0000-0001-5207-5328
  8. Willem Ashwin Mak

    Department of Neuroscience, Erasmus Medical Center, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  9. Marit Runge

    Department of Neuroscience, Erasmus Medical Center, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  10. Francesca Romana Fiocchi

    Department of Neuroscience, Erasmus Medical Center, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  11. Henk-Jan Boele

    Department of Neuroscience, Erasmus Medical Center, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  12. Freek E Hoebeek

    Department of Neuroscience, Erasmus Medical Center, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  13. 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

H2020 European Research Council (ERC-Stg #680235)

  • Martijn Schonewille

ZonMw (ZonMW-451001027)

  • Catarina Osório

Nederlandse Organisatie voor Wetenschappelijk Onderzoek (#016.121.346)

  • Freek E Hoebeek

ZonMw (#91210067)

  • Freek E Hoebeek

C.J. Vaillant Fund

  • Freek E Hoebeek

Nederlandse Organisatie voor Wetenschappelijk Onderzoek (016.Veni.192.270)

  • Joshua J White

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

Reviewing Editor

  1. Ronald L Calabrese, Emory University, United States

Ethics

Animal experimentation: This study was performed under 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 work protocols). All surgeries were performed under isoflurane anesthesia combined with local anesthetics and analgesics in an effort to minimize suffering.

Version history

  1. Received: October 1, 2020
  2. Accepted: May 10, 2021
  3. Accepted Manuscript published: May 11, 2021 (version 1)
  4. Version of Record published: June 11, 2021 (version 2)

Copyright

© 2021, Beekhof 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. Gerrit Cornelis Beekhof
  2. Catarina Osório
  3. Joshua J White
  4. Scott van Zoomeren
  5. Hannah van der Stok
  6. Bilian Xiong
  7. Ingo HMS Nettersheim
  8. Willem Ashwin Mak
  9. Marit Runge
  10. Francesca Romana Fiocchi
  11. Henk-Jan Boele
  12. Freek E Hoebeek
  13. Martijn Schonewille
(2021)
Differential spatiotemporal development of Purkinje cell populations and cerebellum-dependent sensorimotor behaviors
eLife 10:e63668.
https://doi.org/10.7554/eLife.63668

Share this article

https://doi.org/10.7554/eLife.63668

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