Increased levels of D-aspartate in the hippocampus enhance LTP but do not facilitate cognitive flexibility

In the present study, we demonstrate a direct role for D-aspartate in regulating hippocampal synaptic plasticity. These evidences were obtained using two different experimental strategies which enabled a non-physiological increase of endogenous D-aspartate levels in the mouse hippocampus: a genetic approach based on the targeted deletion Of D-aspartate oxidase gene and another based on the oral administration of D-aspartate. Overall, our results indicate that increased D-aspartate content does not affect basal properties of synaptic transmission but enhances long-term potentiation in hippocampal slices from both genetic and pharmacological animal models. Besides electrophysiological data, behavioral analysis suggests that altered levels Of D-aspartate in the hippocampus do not perturb basal spatial learning and memory abilities, but may selectively interfere with the dynamic NMDAR-dependent processes underlying cognitive flexibility. (C) 2007 Elsevier Inc. All rights reserved.