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

Author(s): Piochon, Claire; Kloth, Alexander D; Grasselli, Giorgio; Titley, Heather K; Nakayama, Hisako; et al

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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.
Publication Date:  24
Citation: Piochon, Claire, Kloth, Alexander D, Grasselli, Giorgio, Titley, Heather K, Nakayama, Hisako, Hashimoto, Kouichi, Wan, Vivian, Simmons, Dana H, Eissa, Tahra, Nakatani, Jin, Cherskov, Adriana, Miyazaki, Taisuke, Watanabe, Masahiko, Takumi, Toru, Kano, Masanobu, Wang, Samuel S-H, Hansel, Christian. (Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism. Nat Commun, 5 (5586 - 5586. doi:10.1038/ncomms6586)
DOI: doi:10.1038/ncomms6586
ISSN: 2041-1723
Pages: 5586 - 5586
Type of Material: Journal Article
Journal/Proceeding Title: Nature Communications
Version: Final published version. Article is made available in OAR by the publisher's permission or policy.

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