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

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, Taisuke Miyazaki, Masahiko Watanabe, Toru Takumi, Masanobu Kano, Samuel S.H. Wang, Christian Hansel

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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.

Original languageEnglish (US)
Article number5586
JournalNature communications
Volume5
DOIs
StatePublished - 2014

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Piochon, C., Kloth, A. D., Grasselli, G., Titley, H. K., Nakayama, H., Hashimoto, K., Wan, V., Simmons, D. H., Eissa, T., Nakatani, J., Cherskov, A., Miyazaki, T., Watanabe, M., Takumi, T., Kano, M., Wang, S. S. H., & Hansel, C. (2014). Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism. Nature communications, 5, [5586]. https://doi.org/10.1038/ncomms6586