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Cerebral Cortex Advance Access published online on March 28, 2004
Cerebral Cortex, doi:10.1093/cercor/bhh024
© 2004 by Oxford University Press
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Article

NMDA Receptor Alterations in Neurons from Pediatric Cortical Dysplasia Tissue

Véronique M. André 1, Jorge Flores-Hernández 2, Carlos Cepeda 2*, Amaal J. Starling 2, Snow Nguyen 3, Mary Kay Lobo 2, Harry V. Vinters 4, Michael S. Levine 2, Gary W. Mathern 1

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

* To whom correspondence should be addressed. E-mail: ccepeda{at}mednet.ucla.edu.


  Abstract

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.

Key Words: cerebral cortex, electrophysiology, epilepsy, immunohistochemistry, receptor subunits, RT-PCR


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