Endogenous N-acetylaspartylglutamate reduced NMDA receptor-dependent current neurotransmission in the CA1 area of the hippocampus

Richard Bergeron, Yukio Imamura, John V. Frangioni, Robert W. Greene, Joseph T. Coyle

Research output: Contribution to journalArticle

30 Citations (Scopus)

Abstract

N-Acetylaspartylglutamate (NAAG) is a neuropeptide found in high concentrations in the brain. Using whole-cell recordings of CA1 pyramidal neurons in acute hippocampal slices, we found that either (i) the application of exogenous NAAG or (ii) an increase of endogenous extracellular NAAG, caused by the inhibition of its catabolic enzyme glutamate carboxypeptidase II (GCP II), resulted in a significant reduction in the amplitude of the isolated NMDA receptor (NMDAR) component of the evoked excitatory postsynaptic current (EPSC). Conversely, reduction of endogenous extracellular NAAG caused by either (i) perfusion with a soluble form of pure human GCP II or (ii) affinity purified antibodies against NAAG, enhanced the amplitude of the isolated NMDAR current. Bath application of GCP II inhibitor induced a progressive loss of spontaneous NMDAR miniatures. Furthermore, NAAG blocked the induction of long-term potentiation at Schaffer collateral axons-CA1 pyramidal neuron synapses. All together, these results suggest that NAAG acts as an endogenous modulator of NMDARs in the CA1 area of the hippocampus.

Original languageEnglish (US)
Pages (from-to)346-357
Number of pages12
JournalJournal of Neurochemistry
Volume100
Issue number2
DOIs
StatePublished - Jan 2007

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N-Methyl-D-Aspartate Receptors
Synaptic Transmission
Hippocampus
Glutamate Carboxypeptidase II
Pyramidal Cells
Neurons
Antibody Affinity
Long-Term Potentiation
Excitatory Postsynaptic Potentials
Patch-Clamp Techniques
N-acetyl-1-aspartylglutamic acid
Neuropeptides
Baths
Synapses
Modulators
Axons
Brain
Perfusion
Antibodies
Enzymes

Keywords

  • 2-(phosphonomethyl) pentadioic acid (2-PMPA)
  • GABA
  • Glutamate
  • N-acetylaspartylglutamate (NAAG)
  • Synaptic plasticity
  • Whole-cell patch-clamp

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Endogenous N-acetylaspartylglutamate reduced NMDA receptor-dependent current neurotransmission in the CA1 area of the hippocampus. / Bergeron, Richard; Imamura, Yukio; Frangioni, John V.; Greene, Robert W.; Coyle, Joseph T.

In: Journal of Neurochemistry, Vol. 100, No. 2, 01.2007, p. 346-357.

Research output: Contribution to journalArticle

Bergeron, Richard ; Imamura, Yukio ; Frangioni, John V. ; Greene, Robert W. ; Coyle, Joseph T. / Endogenous N-acetylaspartylglutamate reduced NMDA receptor-dependent current neurotransmission in the CA1 area of the hippocampus. In: Journal of Neurochemistry. 2007 ; Vol. 100, No. 2. pp. 346-357.
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