Potentiation of cerebellar Purkinje cells facilitates whisker reflex adaptation through increased simple spike activity

Abstract

Cerebellar plasticity underlies motor learning. However, how the cerebellum operates to enable learned changes in motor output is largely unknown. We developed a sensory-driven adaptation protocol for reflexive whisker protraction and recorded Purkinje cell activity from crus 1 and 2 of awake mice. Before training, simple spikes of individual Purkinje cells correlated during reflexive protraction with the whisker position without lead or lag. After training, simple spikes and whisker protractions were both enhanced with the spiking activity now leading behavioral responses. Neuronal and behavioral changes did not occur in two cell-specific mouse models with impaired long-term potentiation at their parallel fiber to Purkinje cell synapses. Consistent with cerebellar plasticity rules, increased simple spike activity was prominent in cells with low complex spike response probability. Thus, potentiation at parallel fiber to Purkinje cell synapses may contribute to reflex adaptation and enable expression of cerebellar learning through increases in simple spike activity.

Data availability

Source data files for all box plots are provided, i.e. for Figures 3, 5 and 8 and for Figure supplements 1-S2, 5-S1, 5-S2, 5-S3, 5-S4, 8-S1 and 8-S2.

Article and author information

Author details

  1. Vincenzo Romano

    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:" 0000-0002-4449-6541
  2. Licia De Propris

    Department of Neuroscience, Erasmus Medical Center, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  3. Laurens WJ Bosman

    Department of Neuroscience, Erasmus Medical Center, Rotterdam, Netherlands
    For correspondence
    l.bosman@erasmusmc.nl
    Competing interests
    The authors declare that no competing interests exist.
  4. Pascal Warnaar

    Department of Neuroscience, Erasmus Medical Center, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  5. Michiel Manuel ten Brinke

    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:" 0000-0002-9478-1586
  6. Sander Lindeman

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

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

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

    Department of Neuroscience, Erasmus Medical Center, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  10. Emily Middendorp Guerra

    Department of Neuroscience, Erasmus Medical Center, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  11. Tycho M Hoogland

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

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

    Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy
    Competing interests
    The authors declare that no competing interests exist.
  14. Chris I De Zeeuw

    Department of Neuroscience, Erasmus Medical Center, Rotterdam, Netherlands
    For correspondence
    c.dezeeuw@erasmusmc.nl
    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

Funding

Nederlandse Organisatie voor Wetenschappelijk Onderzoek (ALW)

  • Chris I De Zeeuw

ZonMw

  • Chris I De Zeeuw

European Research Council (ERC-Advanced Grant)

  • Chris I De Zeeuw

European Research Council (ERC-PoC)

  • Chris I De Zeeuw

China Scholarship Council (2010623033)

  • Chiheng Ju

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 experimental procedures were approved a priori by an independent animal ethical committee (DEC-Consult, Soest, The Netherlands) as required by Dutch law and conform the relevant institutional regulations of the Erasmus MC and Dutch legislation on animal experimentation. Permissions were obtained under the following license numbers: EMC2656, EMC2933, EMC2998, EMC3001, EMC3168 and AVD101002015273.

Reviewing Editor

  1. David Kleinfeld, University of California, San Diego, United States

Publication history

  1. Received: June 4, 2018
  2. Accepted: December 17, 2018
  3. Accepted Manuscript published: December 18, 2018 (version 1)
  4. Version of Record published: January 9, 2019 (version 2)

Copyright

© 2018, Romano 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. Vincenzo Romano
  2. Licia De Propris
  3. Laurens WJ Bosman
  4. Pascal Warnaar
  5. Michiel Manuel ten Brinke
  6. Sander Lindeman
  7. Chiheng Ju
  8. Arthiha Velauthapillai
  9. Jochen K Spanke
  10. Emily Middendorp Guerra
  11. Tycho M Hoogland
  12. Mario Negrello
  13. Egidio D Angelo
  14. Chris I De Zeeuw
(2018)
Potentiation of cerebellar Purkinje cells facilitates whisker reflex adaptation through increased simple spike activity
eLife 7:e38852.
https://doi.org/10.7554/eLife.38852
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