IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v5y2014i1d10.1038_ncomms6586.html
   My bibliography  Save this article

Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism

Author

Listed:
  • Claire Piochon

    (University of Chicago)

  • Alexander D. Kloth

    (Princeton University
    Princeton Neuroscience Institute, Princeton University)

  • Giorgio Grasselli

    (University of Chicago)

  • Heather K. Titley

    (University of Chicago)

  • Hisako Nakayama

    (Graduate School of Biomedical and Health Sciences, Hiroshima University)

  • Kouichi Hashimoto

    (Graduate School of Biomedical and Health Sciences, Hiroshima University)

  • Vivian Wan

    (University of Chicago)

  • Dana H. Simmons

    (University of Chicago)

  • Tahra Eissa

    (University of Chicago)

  • Jin Nakatani

    (Shiga University of Medical Science)

  • Adriana Cherskov

    (Princeton University
    Princeton Neuroscience Institute, Princeton University)

  • Taisuke Miyazaki

    (Hokkaido University Graduate School of Medicine)

  • Masahiko Watanabe

    (Hokkaido University Graduate School of Medicine)

  • Toru Takumi

    (RIKEN Brain Science Institute)

  • Masanobu Kano

    (Graduate School of Medicine, The University of Tokyo)

  • Samuel S.-H. Wang

    (Princeton University
    Princeton Neuroscience Institute, Princeton University)

  • Christian Hansel

    (University of Chicago)

Abstract

A common feature of autism spectrum disorder (ASD) is the impairment of motor control and learning, occurring in a majority of children with autism, consistent with perturbation in cerebellar function. Here we report alterations in motor behaviour and cerebellar synaptic plasticity in a mouse model (patDp/+) for the human 15q11-13 duplication, one of the most frequently observed genetic aberrations in autism. These mice show ASD-resembling social behaviour deficits. We find that in patDp/+ mice delay eyeblink conditioning—a form of cerebellum-dependent motor learning—is impaired, and observe deregulation of a putative cellular mechanism for motor learning, long-term depression (LTD) at parallel fibre-Purkinje cell synapses. Moreover, developmental elimination of surplus climbing fibres—a model for activity-dependent synaptic pruning—is impaired. These findings point to deficits in synaptic plasticity and pruning as potential causes for motor problems and abnormal circuit development in autism.

Suggested Citation

  • Claire Piochon & Alexander D. Kloth & Giorgio Grasselli & Heather K. Titley & Hisako Nakayama & Kouichi Hashimoto & Vivian Wan & Dana H. Simmons & Tahra Eissa & Jin Nakatani & Adriana Cherskov & Taisu, 2014. "Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism," Nature Communications, Nature, vol. 5(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6586
    DOI: 10.1038/ncomms6586
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/ncomms6586
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/ncomms6586?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms6586. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.