PT  - JOURNAL ARTICLE
AU  - Anand Suresh
AU  - Anna Dunaevsky
TI  - Impaired AMPARs translocation into dendritic spines with motor skill learning in the Fragile X mouse model
AID  - 10.1523/ENEURO.0364-22.2023
DP  - 2023 Mar 10
TA  - eneuro
PG  - ENEURO.0364-22.2023
4099  - http://www.eneuro.org/content/early/2023/03/09/ENEURO.0364-22.2023.short
4100  - http://www.eneuro.org/content/early/2023/03/09/ENEURO.0364-22.2023.full
AB  - 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 StatementThis 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.