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

Research output: Contribution to journalArticlepeer-review

58 Scopus citations

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
StatePublished - Jan 2005

Keywords

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

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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