NAAG reduces NMDA receptor current in CAl hippocampal pyramidal neurons of acute slices and dissociated neurons

Richard Bergeron, Joseph T. Coyle, Guochan Tsai, Robert W. Greene

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Abstract

N-Acetylaspartylglutamate (NAAG) is an abundant neuropeptide in the nervous system, yet its functions are not well understood. Pyramidal neurons of the CAl sector of acutely prepared hippocampal slices were recorded using the whole-cell patch-clamp technique. At low concentrations (20 μM), NAAG reduced isolated N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic currents or NMDA-induced currents. The NAAG-induced change in the NMDA concentration/ response curve suggested that the antagonism was not competitive. However, the NAAG-induced change in the concentration/response curve for the NMDAR co-agonist, glycine, indicated that glycine can overcome the NAAG antagonism. The antagonism of the NMDAR induced by NAAG was still observed in the presence of LY-341495, a potent and selective mGluRB antagonist. Moreover, in dissociated pyramidal neurons of the CAl region, NAAG also reduced the NMDA current and this effect was reversed by glycine. These results suggest that NAAG reduces the NMDA currents in hippocampal CAl pyramidal neurons.

Original languageEnglish (US)
Pages (from-to)7-16
Number of pages10
JournalNeuropsychopharmacology
Volume30
Issue number1
DOIs
Publication statusPublished - Jan 2005

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Keywords

  • 7-Chlorokynurenic acid
  • Glycine
  • Hippocampus
  • NMDA receptor
  • Patch-clamp
  • Synaptic transmission

ASJC Scopus subject areas

  • Pharmacology

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