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Induction of LTP in the hippocampus needs synaptic activation of glutamate metabotropic receptors

Nature volume 363, pages 347–350 (1993)Cite this article

Abstract

UNDERSTANDING the mechanisms of long-term potentiation (LTP) should provide insights into the molecular basis of learning and memory in vertebrates. lonotropic glutamate receptors play a central role in LTP; AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate) receptors and NMDA (N-methyl-D-aspar-tate) receptors mediate synaptic responses that are enhanced in LTP and, in addition, NMDA receptors are necessary for the induction of LTP in most pathways1. There is also circumstantial evidence that metabotropic glutamate receptors (mGluRs) may be involved in LTP because the specific mGluR agonist aminocyc-lopentane dicarboxylate can augment tetanus-induced LTP2 and, under certain circumstances, can itself induce a slow-onset potentiation3,4. But the absence of any effective mGluR antagonist has prevented the determination of whether mGluRs are involved in the induction of tetanus-induced LTP. We report here that (RS)-α-methyl-4-carboxyphenylglycine is a specific mGluR antagonist in the hippocampus and have used this compound to examine the nature of the involvement of mGluRs in LTP. We show that synaptic activation of mGluRs is necessary for the induction of both NMDA receptor-dependent and NMDA receptor-independent forms of LTP in the hippocampus.

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Author notes

  1. David E. Jane and Jeffrey C. Watkins: Department of Pharmacology, The School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK

Affiliations

  1. Department of Pharmacology, The Medical School, University of Birmingham, Edgbaston, Birmingham, B15 2TT, UK

    Zafar I. Bashir, Zuner A. Bortolotto, Ceri H. Davies, Nicola Berretta, Andrew J. Irving, Andrew J. Seal, Jeremy M. Henley, David E. Jane, Jeffrey C. Watkins & Graham L. Collingridge

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  1. Zafar I. Bashir
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  2. Zuner A. Bortolotto
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  4. Nicola Berretta
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Bashir, Z., Bortolotto, Z., Davies, C. et al. Induction of LTP in the hippocampus needs synaptic activation of glutamate metabotropic receptors. Nature 363, 347–350 (1993). https://doi.org/10.1038/363347a0

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