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Long-lasting enhancement of NMDA receptor-mediated synaptic transmission by metabotropic glutamate receptor activation

Nature volume 367, pages 557–559 (1994)Cite this article

Abstract

SYNAPTIC transmission mediated by the N-methyl-D-aspartate (NMDA) glutamate receptor plays a key role in a range of plastic processes in the nervous system. These include long-term potentiation of synaptic transmission mediated by the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptor, neuronal development, excitotoxicity and certain learning tasks1,2. Recently, long-term potentiation of NMDA receptor-mediated synaptic transmission was found to occur following high-frequency (tetanic) stimulation via an unknown mechanism3–7. We show here that activation of metabotropic glutamate (mGlu) receptors by neurally released transmitter underlies this type of long-term potentiation. The whole-cell patch-clamp technique in the 'thick' slice of the rat dentate gyrus was used to measure NMDA receptor-mediated excitatory postsynaptic currents. We have found that mGlu receptor activation by a selective agonist produced a long-lasting enhancement which was mutually exclusive with long-term potentiation of these NMDA currents. Moreover, both forms of potentiation were greatly reduced by the mGlu receptor antagonists L-2-amino-3-phosphonopropionate and (R,S)-α-methy 1-4-carboxyphenylglycine.

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Author notes

  1. John J. O'Connor

    Present address: Department of Human Anatomy and Physiology, University College Dublin, Earlsford Terrace, Dublin, 2, Ireland

  2. Michael J. Rowan: To whom correspondence should be addressed.

Authors and Affiliations

  1. Department of Pharmacology and Therapeutics,

    John J. O'Connor & Michael J. Rowan

  2. Department of Physiology, Trinity College, Dublin, 2, Ireland

    Roger Anwyl

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  1. John J. O'Connor
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  2. Michael J. Rowan
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  3. Roger Anwyl
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O'Connor, J., Rowan, M. & Anwyl, R. Long-lasting enhancement of NMDA receptor-mediated synaptic transmission by metabotropic glutamate receptor activation. Nature 367, 557–559 (1994). https://doi.org/10.1038/367557a0

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