Synaptic circuit abnormalities of motor-frontal layer 2/3 pyramidal neurons in a mutant mouse model of Rett syndrome

Motor and cognitive functions are severely impaired in Rett syndrome (RTT). Here, we examined local synaptic circuits of layer 2/3 (L2/3) pyramidal neurons in motor-frontal cortex of male hemizygous MeCP2-null mice at 3 to 4 weeks of age. We mapped local excitatory input to L2/3 neurons using glutamate uncaging and laser scanning photostimulation, and compared synaptic input maps recorded from MeCP2-null and wild type (WT) mice. Local excitatory input was significantly reduced in the mutants. The strongest phenotype was observed for lateral (horizontal, intralaminar) inputs, that is, L2/3→2/3 inputs, which showed a large reduction in MeCP2−/y animals. Neither the amount of local inhibitory input to these L2/3 pyramidal neurons nor their intrinsic electrophysiological properties differed by genotype. Our findings provide further evidence that excitatory networks are selectively reduced in RTT. We discuss our findings in the context of recently published parallel studies using selective MeCP2 knockdown in individual L2/3 neurons.