D-Serine differently modulates NMDA receptor function in rat CA1 hippocampal pyramidal cells and interneurons.

The organization of the neuronal hippocampal network depends on the tightly regulated interaction between pyramidal cells (PCs) and interneurons (Ints). NMDA receptor (NMDAR) activation requires the binding of glutamate and co-activation of the 'glycine site'. It has been reported that D-serine is a more potent endogenous agonist than glycine for that site. While many studies have focused on NMDAR function in PCs, little is known regarding the modulation of NMDARs in Ints. We studied the modulatory effect of D-serine on NMDAR EPSCs in PCs and in stratum radiatum Ints using whole-cell patch-clamp recording in rat acute hippocampal slices. We found that D-serine enhances NMDAR function and differently modulates NMDAR currents in both cell types. The augmentation of NMDAR currents by D-serine was significantly larger in PCs compared with Ints. Moreover, we found differences in the kinetics of NMDAR currents in PCs and Ints. Our findings indicate that regulation of NMDAR through the 'glycine site' depends on the cell types. We speculate that the observed differences arise from assemblies of diverse NMDAR subunits. Overall, our data suggest that D-serine may be involved in regulation of the excitation-inhibition balance in the CA1 hippocampal region.