@article{6e9228acf15745cea47318fc873ca60e,
title = "Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism",
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.",
author = "Claire Piochon and Kloth, {Alexander D.} and Giorgio Grasselli and Titley, {Heather K.} and Hisako Nakayama and Kouichi Hashimoto and Vivian Wan and Simmons, {Dana H.} and Tahra Eissa and Jin Nakatani and Adriana Cherskov and Taisuke Miyazaki and Masahiko Watanabe and Toru Takumi and Masanobu Kano and Wang, {Samuel S.H.} and Christian Hansel",
note = "Funding Information: We would like to thank E.H. Cook and P. Mason for helpful suggestions and for critically reading the manuscript. This work was supported by Ministry of Education, Culture, Sports, Science and Technology in Japan Grants-in-Aid for Scientific Research (25242077 and 23111005 to T.T.; 25123716 and 25117006 to K.H.; 2420007 to M.W.; 25000015 to M.K.), and the Ministry{\textquoteright}s Strategic Research Program for Brain Sciences (M.K.), CREST from the Japanese Science and Technology Agency (T.T.), MEXT, Japan (M.K.), the Global COE Program (M.K.), a grant from the Nancy Lurie Marks Family Foundation (S.S.-H.W.), National Institutes of Health grants NS045193 (S.S.-H.W.) and F31 MH098651 (A.K.), Simons Foundation grants SFARI 221582 (S.S.-H.W.), SFARI 203507 and SFARI 311232 (C.H.), and a grant from the Brain Research Foundation BRF SG 2011-07 (C.H.). Publisher Copyright: {\textcopyright} 2014 Macmillan Publishers Limited. All rights reserved.",
year = "2014",
doi = "10.1038/ncomms6586",
language = "English (US)",
volume = "5",
journal = "Nature Communications",
issn = "2041-1723",
publisher = "Nature Publishing Group",
}