Hisako Nakayama
   Department   School of Medicine, School of Medicine
   Position   Associate Professor
Article types Original article
Language English
Peer review Peer reviewed
Title Cerebellar plasticity and motor learning deficits in a copy-number variation mouse model of autism.
Journal Formal name:Nature Communications
Abbreviation:Nat Commun
ISSN code:20411723
Domestic / ForeginForegin
Volume, Issue, Page 5,pp.5586
Author and coauthor 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*
Publication date 2014/11
Summary 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.
DOI 10.1038/ncomms6586
PMID 25418414