title: Increased levels of d-aspartate in the hippocampus enhance LTP but do not facilitate cognitive flexibility.
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.
authors.affiliation: Laboratory of Behavioral Neuroscience, CEINGE Biotecnologie Avanzate, Naples, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Errico
authors.forename: Robert
authors.initials: R
authors.lastname: Nisticò
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Palma
authors.forename: Mauro
authors.initials: M
authors.lastname: Federici
authors.forename: Andrea
authors.initials: A
authors.lastname: Affuso
authors.forename: Elisa
authors.initials: E
authors.lastname: Brilli
authors.forename: Enza
authors.initials: E
authors.lastname: Topo
authors.forename: Diego
authors.initials: D
authors.lastname: Centonze
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bernardi
authors.forename: Yuri
authors.initials: Y
authors.lastname: Bozzi
authors.forename: Antimo
authors.initials: A
authors.lastname: D'Aniello
authors.forename: Roberto
authors.initials: R
authors.lastname: Di Lauro
authors.forename: Nicola B
authors.initials: NB
authors.lastname: Mercuri
authors.forename: Alessandro
authors.initials: A
authors.lastname: Usiello
mesh_terms: D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism* / Q000494:pharmacology; D003071:Cognition / Q000187:drug effects / Q000502:physiology*; D050804:D-Aspartate Oxidase / Q000235:genetics; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D009435:Synaptic Transmission / Q000187:drug effects / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D001224:Aspartic Acid; D050804:D-Aspartate Oxidase