NR2A SUBUNIT EXPRESSION SHORTENS NMDA RECEPTOR SYNAPTIC CURRENTS IN DEVELOPING NEOCORTEX

NMDA receptors play important roles in learning and memory and in scul pting neural connections during development. After the period of peak cortical plasticity, NMDA receptor-mediated EPSCs (NMDAR EPSCs) decrea se in duration, A likely mechanism for this change in NMDA receptor pr operties is the molecular alteration of NMDA receptor structure by reg ulation of NMDA receptor subunit gene expression. The four modulatory NMDAR2A-D (NR2A-D) NMDA receptor subunits are known to alter NMDA rece ptor properties, and the expression of these subunits is regulated dev elopmentally. It is unclear, however, how the four NR2 subunits are ex pressed 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 neuro ns of postnatal neocortex revealed that cells expressing NR2A subunit mRNA had faster NMDAR EPSCs than cells not expressing this subunit, re gardless of postnatal age. Expression of NR2A subunit mRNA in cortical neurons at even low levels seemed sufficient to alter the NMDA recept or time course. The proportion of cells expressing NR2A and displaying fast NMDAR EPSCs increased developmentally, thus providing a molecula r basis for the developmental change in mean NMDAR EPSC duration.