RT Journal Article
SR Electronic
T1 Synaptic Circuit Abnormalities of Motor-Frontal Layer 2/3 Pyramidal Neurons in an RNA Interference Model of Methyl-CpG-Binding Protein 2 Deficiency
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 12440
OP 12448
DO 10.1523/JNEUROSCI.3321-09.2009
VO 29
IS 40
A1 Lydia Wood
A1 Noah W. Gray
A1 Zhaolan Zhou
A1 Michael E. Greenberg
A1 Gordon M. G. Shepherd
YR 2009
UL http://www.jneurosci.org/content/29/40/12440.abstract
AB 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.