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Volume 17, Number 7, Issue of April 1, 1997 pp. 2469-2476
Copyright ©1997 Society for Neuroscience

NR2A Subunit Expression Shortens NMDA Receptor Synaptic Currents in Developing Neocortex

Received Nov. 18, 1996; revised Jan. 17, 1997; accepted Jan. 23, 1997.

Alexander C. Flint¹, Ulrike S. Maisch^{2, 3}, Jochen H. Weishaupt³, Arnold R. Kriegstein^{1, 2}, and Hannah Monyer³

¹ Center for Neurobiology and Behavior and ² Department of Neurology, Columbia University College of Physicians and Surgeons, New York, New York 10032, and ³ Center for Molecular Biology, University of Heidelberg, D-69120 Heidelberg, Germany

NMDA receptors play important roles in learning and memory and in sculpting neural connections during development. After the period of peak cortical plasticity, NMDA receptor-mediated EPSCs (NMDAR EPSCs) decrease in duration. A likely mechanism for this change in NMDA receptor properties is the molecular alteration of NMDA receptor structure by regulation of NMDA receptor subunit gene expression. The four modulatory NMDAR2A-D (NR2A-D) NMDA receptor subunits are known to alter NMDA receptor properties, and the expression of these subunits is regulated developmentally. It is unclear, however, how the four NR2 subunits are expressed in individual neurons and which NR2 subunits are important to the regulation of NMDA receptor properties during development in vivo. Analysis of NR2 subunit gene expression in single characterized neurons of postnatal neocortex revealed that cells expressing NR2A subunit mRNA had faster NMDAR EPSCs than cells not expressing this subunit, regardless of postnatal age. Expression of NR2A subunit mRNA in cortical neurons at even low levels seemed sufficient to alter the NMDA receptor time course. The proportion of cells expressing NR2A and displaying fast NMDAR EPSCs increased developmentally, thus providing a molecular basis for the developmental change in mean NMDAR EPSC duration.

Key words: NMDA receptors; ion channel subunit expression; single-cell RT-PCR; dot-blot hybridization; phosphorimager analysis; patch clamp; neocortical development; neocortical physiology; synaptic transmission; EPSCs

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