Abstract
Motor skill learning induces changes in synaptic structure and function in the primary motor cortex. In the Fragile X Syndrome (FXS) mouse model an impairment in motor skill learning and associated formation of new dendritic spines was previously reported. However, whether modulation of synaptic strength through trafficking of AMPA receptors with motor skill training is impaired in FXS is not known. Here we performed in vivo imaging of a tagged AMPA receptor subunit, GluA2, in layer (L) 2/3 neurons in the primary motor cortex of wild type and Fmr1 KO male mice at different stages of learning a single forelimb-reaching task. Surprisingly, in the Fmr1 KO mice, despite impairments in learning there was no deficit in motor skill training-induced spine formation. However, the gradual accumulation of GluA2 in WT stable spines, which persists after training is completed and past the phase of spine number normalization, is absent in the Fmr1 KO mouse. These results demonstrate that motor skill learning not only reorganizes circuits through formation of new synapses, but also strengthens existing synapses through accumulation of AMPA receptors and GluA2 changes are better associated with learning than new spine formation.
Significance Statement
This study identifies a significant synaptic defect associated with a behavioral impairment relevant to the pathology of Fragile X syndrome (FXS). Using in vivo imaging of a tagged AMPA-type receptor subunit GluA2, we found that the motor-skill training-induced accumulation of GluA2 in dendritic spines that occurs in control mice is impaired in the Fmr1 knock out (KO) mouse. This study identifies a synaptic correlate of impaired motor skill learning in the Fmr1 KO mouse.
Footnotes
Authors report no competing interests.
This work was supported by R01HD067218 and R01NS109381 to A.D. and American Heart Association Predoctoral Fellowship 15PRE23280027 to
This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
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