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Cerebral Cortex Advance Access originally published online on March 28, 2004
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Cerebral Cortex June 2004; 14:634-646
© Oxford University Press 2004

Article

NMDA Receptor Alterations in Neurons from Pediatric Cortical Dysplasia Tissue

Véronique M. André1,2,*, Jorge Flores-Hernández1,4,*, Carlos Cepeda1, Amaal J. Starling1, Snow Nguyen2, Mary Kay Lobo1, Harry V. Vinters3, Michael S. Levine1 and Gary W. Mathern1,2

1 Mental Retardation Research Center, David Geffen School of Medicine, University of California, Los Angeles, CA, USA, 2 Division of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles, CA, USA, 3 Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

4 Present address: Institute of Physiology, Benemérita Universidad Autónoma de Puebla, Puebla City, PC 72000, Mexico

* These authors contributed equally to this study.

The subunit composition of glutamate receptors affects their functional properties, and could contribute to abnormal electrophysiology in pediatric cortical dysplasia (CD). We examined electrophysiological responses and subunit assembly of N-methyl-D-aspartate (NMDA) receptors in acutely dissociated normal-appearing pyramidal and cytomegalic neurons from CD tissue and normal-appearing pyramidal neurons from non-CD tissue. In most cytomegalic and ~30% of normal-appearing pyramidal neurons from CD tissue, NMDA currents showed decreased Mg2+ sensitivity compared with neurons from non-CD tissue. Ifenprodil had less effect in CD compared with non-CD neurons, indicating a functional loss of NR2B subunits. NMDA-evoked current density was decreased in cytomegalic compared with normal-appearing neurons. Single-cell reverse transcriptase polymerase chain reaction showed that all non-CD neurons expressed NR2B subunit mRNA. By comparison, 22% of pyramidal neurons in CD tissue lacked NR2B mRNA. Immunofluorescence showed a decrease in NR2B subunit expression in cytomegalic neurons and a subset of normal-appearing pyramidal neurons from CD tissue. Taken together, these results demonstrate the presence of NMDA receptors with altered subunit composition and Mg2+ sensitivity that could contribute to functional abnormalities in CD.


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