@article {Wood12440, author = {Lydia Wood and Noah W. Gray and Zhaolan Zhou and Michael E. Greenberg and Gordon M. G. Shepherd}, title = {Synaptic Circuit Abnormalities of Motor-Frontal Layer 2/3 Pyramidal Neurons in an RNA Interference Model of Methyl-CpG-Binding Protein 2 Deficiency}, volume = {29}, number = {40}, pages = {12440--12448}, year = {2009}, doi = {10.1523/JNEUROSCI.3321-09.2009}, publisher = {Society for Neuroscience}, abstract = {Rett syndrome, an autism spectrum disorder with prominent motor and cognitive features, results from mutations in the gene for methyl-CpG-binding protein 2 (MeCP2). Here, to identify cortical circuit abnormalities that are specifically associated with MeCP2 deficiency, we used glutamate uncaging and laser scanning photostimulation to survey intracortical networks in mouse brain slices containing motor-frontal cortex. We used in utero transfection of short hairpin RNA constructs to knock down MeCP2 expression in a sparsely distributed subset of layer (L) 2/3 pyramidal neurons in wild-type mice, and compared input maps recorded from transfected-untransfected pairs of neighboring neurons. The effect of MeCP2 deficiency on local excitatory input pathways was severe, with an average reduction in excitatory synaptic input from middle cortical layers (L3/5A) of \>30\% compared with MeCP2-replete controls. MeCP2 deficiency primarily affected the strength, rather than the topography, of excitatory intracortical pathways. Inhibitory synaptic inputs and intrinsic eletrophysiological properties were unaffected in the MeCP2-knockdown neurons. These studies indicate that MeCP2 deficiency in individual postsynaptic cortical pyramidal neurons is sufficient to induce a pathological synaptic defect in excitatory intracortical circuits.}, issn = {0270-6474}, URL = {https://www.jneurosci.org/content/29/40/12440}, eprint = {https://www.jneurosci.org/content/29/40/12440.full.pdf}, journal = {Journal of Neuroscience} }