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

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

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

2014
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Overview
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. Impairments of cerebellar-dependent motor control and learning are implicated in some forms of autism spectrum disorder (ASD). In this study, the authors provide a characterization of the motor deficits and cerebellar function abnormalities in a transgenic mouse model of ASD.