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.
Errico
Francesco
F
Laboratory of Behavioral Neuroscience, CEINGE Biotecnologie Avanzate, Naples, Italy.
Nisticò
Robert
R
Palma
Giuseppe
G
Federici
Mauro
M
Affuso
Andrea
A
Brilli
Elisa
E
Topo
Enza
E
Centonze
Diego
D
Bernardi
Giorgio
G
Bozzi
Yuri
Y
D'Aniello
Antimo
A
Di Lauro
Roberto
R
Mercuri
Nicola B
NB
Usiello
Alessandro
A
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
D001224:Aspartic Acid; D050804:D-Aspartate Oxidase