Distinct NMDA receptor subpopulations contribute to long-term potentiation and long-term depression induction.

S. Hrabetova, P. Serrano, N. Blace, H. W. Tse, D. A. Skifter, D. E. Jane, Daniel T Monaghan, T. C. Sacktor

Research output: Contribution to journalArticle

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Abstract

Long-term potentiation (LTP) and long-term depression (LTD) are persistent modifications of synaptic strength that have been implicated in learning, memory, and neuronal development. Despite their opposing effects, both forms of plasticity can be triggered by the activation of NMDA receptors. One mechanism proposed for this bidirectional response is that the specific patterns of afferent stimulation producing LTP and LTD activate to different degrees a uniform receptor population. A second possibility is that these patterns activate separate receptor subpopulations composed of different NMDA receptor (NR) subunits. To test this hypothesis we examined the inhibition of LTP and LTD by a series of competitive NMDA receptor antagonists that varied in their affinities for NR2A/B and NR2C/D subunits. The potency for the inhibition of LTP compared with inhibition of LTD varied widely among the agents. Antagonists with higher affinity for NR2A/B subunits relative to NRC/D subunits showed more potent inhibition of LTP than of LTD. D-3-(2-carboxypiperazine-4-yl)-1-propenyl-1-phosphonic acid, which binds to NR2A/B with very high affinity relative to NR2C/D, showed an approximately 1000-fold higher potency for LTP than for LTD. These results show that distinct subpopulations of NMDA receptors characterized by different NR2 subunits contribute to the induction mechanisms of potentiation and depression.

Original languageEnglish (US)
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
Volume20
Issue number12
StatePublished - Jan 1 2000
Externally publishedYes

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Long-Term Potentiation
N-Methyl-D-Aspartate Receptors
Depression
Learning
Inhibition (Psychology)
Population

ASJC Scopus subject areas

  • Neuroscience(all)

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Distinct NMDA receptor subpopulations contribute to long-term potentiation and long-term depression induction. / Hrabetova, S.; Serrano, P.; Blace, N.; Tse, H. W.; Skifter, D. A.; Jane, D. E.; Monaghan, Daniel T; Sacktor, T. C.

In: The Journal of neuroscience : the official journal of the Society for Neuroscience, Vol. 20, No. 12, 01.01.2000.

Research output: Contribution to journalArticle

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AU - Hrabetova, S.

AU - Serrano, P.

AU - Blace, N.

AU - Tse, H. W.

AU - Skifter, D. A.

AU - Jane, D. E.

AU - Monaghan, Daniel T

AU - Sacktor, T. C.

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