N-Methyl-D-aspartate receptor plasticity in kindling: Quantitative and qualitative alterations in the N-methyl-D-aspartate receptor-channel complex

G. C. Yeh, D. W. Bonhaus, J. V. Nadler, J. O. McNamara

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Kindling is an animal model of epilepsy and neuronal plasticity produced by periodic electrical stimulation of the brain. Electrophysiologic studies indicate that this phenomenon is associated with increased participation of N-methyl-D-aspartate (NMDA) receptors in excitatory synaptic transmission. Biochemical studies suggest that a change intrinsic to the NMDA receptor-channel complex may contribute to the increase in NMDA receptor mediated synaptic transmission. We tested this idea by measuring the binding of 3-[(+)-2-(carboxypiperazin-4-yl)][1,2-3H]propyl-1-phosphonic acid ([3H]CPP), [3H]glycine, and tritiated N-[(1-thienyl)cyclohexyl]piperidine ([3H]TCP) to rat hippocampal membranes. In this preparation these ligands are selective for the NMDA receptor, the strychnine-insensitive glycine receptor, and the NMDA receptor-gated ion channel, respectively. Kindling increased the density of CPP, glycine, and TCP binding sites in hippocampal membranes by 47%, 42%, and 25%, respectively. No significant changes were detected in the affinity of these binding sites. Surprisingly, alterations in the glycine binding site were detected in animals sacrificed 1 month but not 1 day after the final kindling stimulation. Thus, delayed upregulation of the NMDA receptor-channel complex may be one molecular mechanism that maintains the long-lasting hyperexcitability of hippocampal neurons in kindled animals.

Original languageEnglish
Pages (from-to)8157-8160
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number20
Publication statusPublished - 1989
Externally publishedYes


ASJC Scopus subject areas

  • General
  • Genetics

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