Synaptic Circuit Abnormalities of Motor-Frontal Layer 2/3 Pyramidal Neurons in an RNA Interference Model of Methyl-CpG-Binding Protein 2 Deficiency

Wood, L., Gray, N. W., Zhou, Z. L., Greenberg, M. E., Shepherd, G. M. G. (October 2009) Synaptic Circuit Abnormalities of Motor-Frontal Layer 2/3 Pyramidal Neurons in an RNA Interference Model of Methyl-CpG-Binding Protein 2 Deficiency. J Neurosci, 29 (40). pp. 12440-12448. ISSN 0270-6474

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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.

Item Type:	Paper
Uncontrolled Keywords:	RAT BARREL CORTEX RETT-SYNDROME BDNF TRANSCRIPTION GENE-TRANSFER MOUSE MODEL MECP2 MICE ELECTROPORATION ORGANIZATION PLASTICITY
Subjects:	diseases & disorders > congenital hereditary genetic diseases Investigative techniques and equipment Investigative techniques and equipment > RNAI organs, tissues, organelles, cell types and functions > tissues types and functions > barrel cortex organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions > cell types organs, tissues, organelles, cell types and functions > cell types and functions organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons organs, tissues, organelles, cell types and functions organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons > pyramidal neurons organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons > pyramidal neurons organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons > pyramidal neurons organs, tissues, organelles, cell types and functions > tissues types and functions
CSHL Authors:	Gray, Noah W.
Communities:	CSHL labs > Svoboda lab
Depositing User:	Matt Covey
Date:	7 October 2009
Date Deposited:	19 Feb 2013 19:36
Last Modified:	06 Nov 2017 20:55
PMCID:	PMC2782478
Related URLs:	Publisher
URI:	https://repository.cshl.edu/id/eprint/27465

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