GluA and GluN receptors regulate the surface density of GluN receptor subunits in cultured neocortical interneurons

J. Neurochem. (2012) 121, 597–606. In cultured rat neocortical interneurons, we have studied the effect of long‐term application of NMDA or AMPA on the surface density of the NMDA (GluN) receptor subunits GluN1 and GluN2B. Stimulation of Ca2+‐permeable AMPA (GluA) receptors located on the interneurons decreased the response of GluN receptors. The reduction was caused by a decrease in the surface density of GluN1/GluN2B subunits. In contrast, stimulation of GluN receptors located on the interneurons enhanced the surface density of GluN1/GluN2B subunits. Both effects could be induced by network activation. “GluA and GluN receptors regulate the surface density of GluN receptor subunits in cultured neocortical interneurons” We studied how long‐term application of 5 μM NMDA reduced the surface GluN1/GluN2B subunits in GluN receptors in cultured neocortical interneurons. NMDA seemed to exert two actions. It enhanced the surface density of GluN1/GluN2B subunits by stimulating GluN receptors located on the neurons. Via network activation NMDA additionally caused the release of glutamate which acted on Ca2+‐permeable AMPA (GluA) receptors which reduced the surface density of GluN1/GluN2B subunits by enhancing receptor endocytosis. Conclusion: the long‐term regulation of GluN receptors by glutamate receptors in interneurons is shown for the first time.