1. Increased levels of d-aspartate in the hippocampus enhance LTP but do not facilitate cognitive flexibility
- Author
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Antimo D'Aniello, Andrea Affuso, Francesco Errico, Giorgio Bernardi, Alessandro Usiello, Nicola Biagio Mercuri, Giuseppe Palma, Enza Topo, Diego Centonze, Mauro Federici, Robert Nisticò, Roberto Di Lauro, Elisa Brilli, Yuri Bozzi, Errico, Francesco, Nistico, R., Palma, G., Federici, M., Affuso, A., Brilli, E., Topo, E., Centonze, D., Bernardi, G., Bozzi, Y., D'Aniello, A., DI LAURO, Roberto, Mercuri, N., Usiello, A., Errico, F, Nisticò, R, Palma, G, Federici, M, Affuso, A, Brilli, E, Topo, E, Centonze, D, Bernardi, G, Bozzi, Y, D'Aniello, A, DI LAURO, R, Mercuri, N, and Usiello, Alessandro
- Subjects
Male ,D-Aspartate Oxidase ,GLUTAMATE-RECEPTOR ,endocrine system diseases ,Hippocampus ,Morris water navigation task ,OXIDASE-DEFICIENT MICE ,Hippocampal formation ,Inbred C57BL ,Synaptic Transmission ,Mice ,Cognition ,SYNAPTIC PLASTICITY ,genetics ,Animals, Aspartic Acid ,metabolism/pharmacology, Cognition ,drug effects/physiology, D-Aspartate Oxidase ,genetics, Hippocampus ,drug effects/metabolism, Long-Term Potentiation ,drug effects/genetics, Male, Maze Learning ,drug effects/physiology, Memory Disorders ,genetics/metabolism/physiopathology, Memory ,drug effects/physiology, Mice, Mice ,Inbred C57BL, Mice ,Knockout, Organ Culture Techniques, Synaptic Transmission ,drug effects/genetics, Up-Regulation ,drug effects/genetics ,Mice, Knockout ,Maze Learning ,Animals ,Organ Culture Techniques ,Up-Regulation ,Aspartic Acid ,Long-Term Potentiation ,Memory ,Memory Disorders ,Mice, Inbred C57BL ,Settore BIO/14 ,Cognitive flexibility ,Long-term potentiation ,metabolism/pharmacology ,AMINO-ACID ,NMDA receptor ,LONG-TERM POTENTIATION ,D-SERINE ,Morris water maze ,hormones, hormone substitutes, and hormone antagonists ,Knockout ,Neurotransmission ,Biology ,RAT-BRAIN ,Cellular and Molecular Neuroscience ,Molecular Biology ,RELEASE ,genetics/metabolism/physiopathology ,MEMORY ,nutritional and metabolic diseases ,Cell Biology ,Electrophysiology ,drug effects/physiology ,NMDA ,Hippocamu ,drug effects/metabolism ,Neuroscience ,d-aspartate - Abstract
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. 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. © 2007 Elsevier Inc. All rights reserved.
- Published
- 2008