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Endogenous N ‐acetylaspartylglutamate reduced NMDA receptor‐dependent current neurotransmission in the CA1 area of the hippocampus 1
Author(s) -
Bergeron Richard,
Imamura Yukio,
Frangioni John V.,
Greene Robert W.,
Coyle Joseph T.
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04253.x
Subject(s) - nmda receptor , excitatory postsynaptic potential , long term potentiation , neurotransmission , hippocampus , neuroscience , postsynaptic potential , hippocampal formation , glutamate receptor , schaffer collateral , extracellular , endogeny , biology , neuropeptide , chemistry , receptor , endocrinology , biochemistry , inhibitory postsynaptic potential
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.