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

Francesco Errico, Robert Nisticò, Giuseppe Palma, Mauro Federici, Andrea Affuso, Elisa Brilli, Enza Topo, Diego Centonze, Giorgio Bernardi, Yuri Bozzi, Antimo D'Aniello, Roberto Di Lauro, Nicola B. Mercuri, Alessandro Usiello

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)236-246
Number of pages11
JournalMolecular and Cellular Neuroscience
Issue number2
Publication statusPublished - Feb 2008


  • Cognitive flexibility
  • d-aspartate
  • Hippocamus
  • Long-term potentiation
  • Morris water maze
  • NMDA receptors

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Developmental Neuroscience


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