Dynamic modulation of activity in cerebellar nuclei neurons during pavlovian eyeblink conditioning in mice

  1. Michiel Manuel ten Brinke
  2. Shane Heiney
  3. Xiaolu Wang
  4. Martina Proietti-Onori
  5. Henk-Jan Boele
  6. Jacob Bakermans
  7. Javier F Medina  Is a corresponding author
  8. Zhenyu Gao  Is a corresponding author
  9. Chris I De Zeeuw
  1. Erasmus Medical Center, Netherlands
  2. Baylor College of Medicine, United States

Abstract

While research on the cerebellar cortex is crystallizing our understanding of its function in learning behavior, many questions surrounding its downstream targets remain. Here, we evaluate the dynamics of cerebellar interpositus nucleus (IpN) neurons over the course of Pavlovian eyeblink conditioning. A diverse range of learning-induced neuronal responses was observed, including increases and decreases in activity during the generation of conditioned blinks. Trial-by-trial correlational analysis and optogenetic manipulation demonstrate that facilitation in the IpN drives the eyelid movements. Adaptive facilitatory responses are often preceded by acquired transient inhibition of IpN activity that, based on latency and effect, appear to be driven by complex spikes in cerebellar cortical Purkinje cells. Likewise, during reflexive blinks to periocular stimulation, IpN cells show excitation-suppression patterns that suggest a contribution of climbing fibers and their collaterals. These findings highlight the integrative properties of subcortical neurons at the cerebellar output stage mediating conditioned behavior.

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The following data sets were generated

Article and author information

Author details

  1. Michiel Manuel ten Brinke

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

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Xiaolu Wang

    Department of Neuroscience, Erasmus Medical Center, Rotterdam, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
  4. Martina Proietti-Onori

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

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

    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:" 0000-0003-1645-2645
  7. Javier F Medina

    Department of Neuroscience, Baylor College of Medicine, Houston, United States
    For correspondence
    jfmedina@bcm.edu
    Competing interests
    The authors declare that no competing interests exist.
  8. Zhenyu Gao

    Department of Neuroscience, Erasmus Medical Center, Rotterdam, Netherlands
    For correspondence
    z.gao@erasmusmc.nl
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4979-2366
  9. Chris I De Zeeuw

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

Funding

Nederlandse Organisatie voor Wetenschappelijk Onderzoek

  • Zhenyu Gao

European Research Council

  • Chris I De Zeeuw

National Institutes of Health

  • Javier F Medina

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

Ethics

Animal experimentation: The experiments were approved by the institutional animal welfare committee (Erasmus MC, Rotterdam, The Netherlands). All surgery was performed under isoflurane anaesthesia, and every effort was made to minimize suffering.

Reviewing Editor

  1. Naoshige Uchida, Harvard University, United States

Publication history

  1. Received: May 1, 2017
  2. Accepted: December 6, 2017
  3. Accepted Manuscript published: December 15, 2017 (version 1)
  4. Version of Record published: January 9, 2018 (version 2)

Copyright

© 2017, ten Brinke 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. Michiel Manuel ten Brinke
  2. Shane Heiney
  3. Xiaolu Wang
  4. Martina Proietti-Onori
  5. Henk-Jan Boele
  6. Jacob Bakermans
  7. Javier F Medina
  8. Zhenyu Gao
  9. Chris I De Zeeuw
(2017)
Dynamic modulation of activity in cerebellar nuclei neurons during pavlovian eyeblink conditioning in mice
eLife 6:e28132.
https://doi.org/10.7554/eLife.28132

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