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Hippocampus-dependent learning facilitated by a monoclonal antibody or D-cycloserine

Nature volume 359, pages 638–641 (1992)Cite this article

Abstract

PERSISTENT neuronal plasticity, including that observed at some hippocampal synapses, requires N-methyl-D-aspartate (NMDA)-mediated transmission. NMDA receptor activation may be necessary for hippocampus-dependent learning as antagonists block acquisition in many such tasks. The behavioural effects of NMDA agonists are less well defined. We have shown that a monoclonal antibody (B6B21) displaced [3H]-glycine that was bound specifically to the NMDA receptor, and enhanced the opening of its integral cation channel in a glycine-like fashion, effects that were competitively antagonized by 7-chlorokynurenic acid1. B6B21 also enhanced long-term potentiation in hippocampal slices1. We report here that intraventricular infusions of B6B21 significantly enhances acquisition rates in hippocampus-dependent trace eye blink conditioning in rabbits, halving the number of trials required to reach a criterion of 80% conditioned responses. Peripheral injections of D-cycloserine, a partial agonist of the glycine site on the NMDA receptor which crosses the blood–brain barrier, also doubles rabbits' learning rates. Pseudoconditioning control experiments indicated a lack of nonspecific behavioural sensitization effects. Our data suggest that enhanced activation of the glycine coagonist site on the NMDA receptor/channel complex facilitates one form of associative learning and may be used in other learning tasks.

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Authors and Affiliations

  1. Department of Cell, Molecular and Structural Biology, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, Illinois, 60611-3008, USA

    Lucien T. Thompson, Joseph R. Moskal & John F. Disterhoft

  2. The Chicago Institute for Neurosurgery and Neuroresearch, 428 West Deming Place, Chicago, Illinois, 60614, USA

    Joseph R. Moskal

Authors
  1. Lucien T. Thompson
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  2. Joseph R. Moskal
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  3. John F. Disterhoft
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Thompson, L., Moskal, J. & Disterhoft, J. Hippocampus-dependent learning facilitated by a monoclonal antibody or D-cycloserine. Nature 359, 638–641 (1992). https://doi.org/10.1038/359638a0

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