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.
authors.affiliation: Department of Neurobiology, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Piochon
authors.affiliation: 1] Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA [2] Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Kloth
authors.affiliation: Department of Neurobiology, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Grasselli
authors.affiliation: Department of Neurobiology, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Heather K
authors.initials: HK
authors.lastname: Titley
authors.affiliation: Department of Neurophysiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
authors.forename: Hisako
authors.initials: H
authors.lastname: Nakayama
authors.affiliation: Department of Neurophysiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.
authors.forename: Kouichi
authors.initials: K
authors.lastname: Hashimoto
authors.affiliation: Department of Neurobiology, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Vivian
authors.initials: V
authors.lastname: Wan
authors.affiliation: Department of Neurobiology, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Dana H
authors.initials: DH
authors.lastname: Simmons
authors.affiliation: Department of Neurobiology, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Tahra
authors.initials: T
authors.lastname: Eissa
authors.affiliation: Shiga University of Medical Science, Ohtsu 520-2192, Japan.
authors.forename: Jin
authors.initials: J
authors.lastname: Nakatani
authors.affiliation: 1] Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA [2] Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: Adriana
authors.initials: A
authors.lastname: Cherskov
authors.affiliation: Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Miyazaki
authors.affiliation: Department of Anatomy, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: RIKEN Brain Science Institute, Wako 351-0198, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Takumi
authors.affiliation: Department of Neurophysiology, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan.
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kano
authors.affiliation: 1] Department of Molecular Biology, Princeton University, Princeton, New Jersey 08544, USA [2] Princeton Neuroscience Institute, Princeton University, Princeton, New Jersey 08544, USA.
authors.forename: Samuel S-H
authors.initials: SS
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Hansel
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000503:physiopathology*; D001767:Blinking / Q000502:physiology*; D002531:Cerebellum / Q000502:physiology; D056915:DNA Copy Number Variations / Q000235:genetics*; D004195:Disease Models, Animal; D004594:Electrophysiology; D007858:Learning / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009043:Motor Activity / Q000235:genetics / Q000502:physiology*; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011689:Purkinje Cells / Q000502:physiology; D013569:Synapses / Q000502:physiology