MeCP2 deletion impaired layer 2/3-dominant dynamic reorganization of cortical circuit during motor skill learning

Motor cortex displays remarkable plasticity during motor learning. However, it remains largely unknown how the highly dynamic motor cortical circuit reorganizes during reward-independent procedural learning at the populational level. Machine learning-based analysis of the neuronal events recorded with in vivo two-photon calcium imaging revealed procedural learning-induced circuit reorganization in superficial but not deep layers of the motor cortex while mice learned to run on a speed-controlled treadmill. Mice lacking Methyl-CpG-binding protein (MeCP2), an animal model for Rett Syndrome, exhibited impaired both procedural learning and dynamic circuit reorganization in layer 2/3, but not layer 5a. These results identify potential circuit mechanisms underlying motor skill learning disability caused by MeCP2 deletion and provide insight in developing therapies for Rett syndrome.