Abstract
D-serine which is thought to facilitate the NMDA receptor, present in the forebrain and co-localize with N-methyl-D-aspartate (NMDA) receptor. We reported that the spatial learning in the water maze and tetanus induced hippocampal LTP in the slice preparations were facilitated in the mutant mice lacking D-amino-acid oxidase, an enzyme which metabolizes D-serine. In the present report, we compared NMDA dependent synaptic current and the effect of D-serine on NMDA dependent synaptic current in the hippocampal CA1 area between the wild-type mice and mutant mice lacking D-amino-acid oxidase, to clarify whether NMDA dependent synaptic current was enhanced in the mutant mice and whether the enhancement was D-serine dependent. Excitatory postsynaptic currents (EPSCs) were recorded in CA1 pyramidal cells using whole cell patch-clamp techniques by stimulating Schaffer collateral-commissural fibers of the hippocampal slices. The ratio of NMDA receptor-mediated EPSC amplitudes to non-NMDA receptor-mediated EPSC amplitudes was significantly larger in the mutant mice than in wild-type mice. The ratio of NMDA component to non-NMDA component of the wild-type mice was significantly increased to the levels observed in the mutant mice, when D-serine was added to perfusion medium. We suggest that D-serine increased in the mutant mice brain facilitates NMDA-mediated synaptic current. [J Physiol Sci. 2006;56 Suppl:S163]
