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The Journal of Neuroscience, 0000, 20:RC81:1-6

RAPID COMMUNICATION
Distinct NMDA Receptor Subpopulations Contribute to Long-Term Potentiation and Long-Term Depression Induction

Sabina Hrabetova¹, Peter Serrano¹, Nancy Blace¹, Heong W. Tse², Donald A. Skifter³, David E. Jane², Daniel T. Monaghan³, and Todd Charlton Sacktor¹

¹ Laboratory of Molecular Neuroscience, Departments of Physiology, Pharmacology, and Neurology, State University of New York, Downstate Medical Center, Brooklyn, New York 11203, ² Department of Pharmacology, University of Bristol, School of Medical Sciences, Bristol BS81TD, United Kingdom, and ³ Department of Pharmacology, University of Nebraska Medical Center, Omaha, Nebraska 68198

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 ~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.

Key words: NMDA; NR2 subunit; long-term potentiation; long-term depression; D-3-(2-carboxypiperazine-4-yl)-1-propenyl-1-phosphonic acid; D-2-amino-5-phosphonovaleric acid; (±)-cis-1-(phenanthren-2-yl-carbonyl)piperazine-2,3-dicarboxylic acid

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Copyright © 0000 Society for Neuroscience  0270-6474/00/$05.00/0

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