INCREASED NMDA CURRENT AND SPINE DENSITY IN MICE LACKING THE NMDA RECEPTOR SUBUNIT NR3A

The NMDA (N-methyl-D-aspartate) subclass of glutamate receptor(1) is e ssential for the synaptic plasticity thought to underlie learning and memory(2-4) and for synaptic refinement during development(5,6). It is currently believed that the NMDA receptor (NMDAR) is a heteromultimer ic channel comprising the ubiquitous NR1 subunit and at least one regi onally localized NR2 subunit(7-11). Here we report the characterizatio n of a regulatory NMDAR subunit, NR3A (formerly termed NMDAR-L or chi- 1), which is expressed primarily during brain development(12,13) NR3A co-immunoprecipitates with receptor subunits NR1 and NR2 in cerebrocor tical extracts. In single-channel recordings from Xenopus oocytes, add ition of NR3A to NR1 and NR2 leads to the appearance of a smaller unit ary conductance, Genetic knockout of NR3A in mice results in enhanced NMDA responses and increased dendritic spines in early postnatal cereb rocortical neurons. These data suggest that NR3A is involved in the de velopment of synaptic elements by modulating NMDAR activity.