CHANGING SUBUNIT COMPOSITION OF HETEROMERIC NMDA RECEPTORS DURING DEVELOPMENT OF RAT CORTEX

ACTIVATION Of the N-methyl-D-aspartate (NMDA) receptor is important fo r certain forms of activity-dependent synaptic plasticity, such as lon g-term potentiation (reviewed in ref. 1), and the patterning of connec tions during development of the visual system (reviewed in refs 2, 3). Several subunits of the NMDA receptor have been cloned: these are NMD AR1 (NR1), and NMDAR2A, 2B, 2C and 2D (NR2A-D)(4-8). Based on heterolo gous co-expression studies, it is inferred that NR1 encodes an essenti al subunit of NMDA receptors and that functional diversity of NMDA rec eptors in vivo is effected by differential incorporation of subunits N R2A-NR2D(5-8). Little is known, however, about the actual subunit comp osition or heterogeneity of NMDA receptors in the brain. By co-immunop recipitation with subunit-specific antibodies, we present here direct evidence that NMDA receptors exist in rat neocortex as heteromeric com plexes of considerable heterogeneity, some containing both NR2A and NR 2B subunits. A progressive alteration in subunit composition seen post natally could contribute to NMDA-receptor variation and changing synap tic plasticity during cortical development.