Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism. Author Claire Piochon, Alexander Kloth, Giorgio Grasselli, Heather Titley, Hisako Nakayama, Kouichi Hashimoto, Vivian Wan, Dana Simmons, Tahra Eissa, Jin Nakatani, Adriana Cherskov, Taisuke Miyazaki, Masahiko Watanabe, Toru Takumi, Masanobu Kano, Samuel Wang, Christian Hansel Publication Year 2014 Type Journal Article 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. Keywords Animals, Autistic Disorder, Cerebellum, Disease Models, Animal, Mice, Purkinje Cells, Mice, Inbred C57BL, Patch-Clamp Techniques, Synapses, Learning, Electrophysiology, Neuronal Plasticity, Blinking, DNA Copy Number Variations, Mice, Transgenic, Motor Activity Journal Nat Commun Volume 5 Pages 5586 Date Published 2014 Nov 24 ISSN Number 2041-1723 DOI 10.1038/ncomms6586 Alternate Journal Nat Commun PMCID PMC4243533 PMID 25418414 PubMedPubMed CentralGoogle ScholarBibTeXEndNote X3 XML