Cerebellar Plasticity and Motor Learning Deficits in A Copy Number Variation Mouse Model of Autism

Claire Piochon; Alexander D Kloth; Giorgio Grasselli; Heather K Titley; Hisako Nakayama; Kouichi Hashimoto; Vivian Wan; Dana H Simmons; Tahra Eissa; Jin Nakatani; Adriana Cherskov; Taisuke Miyazaki; Masahiko Watanabe; Toru Takumi; Masanobu Kano; Samuel S-H Wang; Christian Hansel;

RELATED

Related Papers     Patents    Grants    Venues    Experts    Cite    Share    Save

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 behavior 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 behavior 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 fiber-Purkinje cell synapses. Moreover, developmental elimination of surplus climbing fibers—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.

 Paraphrase     Questionfy     Wikify     Simplify     Summarize

Download