Fragile X Syndrome is the most common inherited intellectual disability, and Fragile X Syndrome patients often exhibit motor and learning deficits. It was previously shown that the fmr1 knock-out mice, a common mouse model of Fragile X Syndrome, recapitulates this motor learning deficit and that the deficit is associated with altered plasticity of dendritic spines. Here, we investigated the motor learning-induced turnover, stabilization and clustering of dendritic spines in the fmr1 knock-out mouse using a single forelimb reaching task and in vivo multiphoton imaging. We report that fmr1 knock-out mice have deficits in motor learning-induced changes in dendritic spine turnover and new dendritic spine clustering, but not the motor learning-induced long-term stabilization of new dendritic spines. These results suggest that a failure to establish the proper synaptic connections in both number and location, but not the stabilization of the connections that are formed, contributes to the motor learning deficit seen in the fmr1 knock-out mouse.
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