Glutamate-receptor-mediated encoding and retrieval of paired-associate learning (original) (raw)

Nature volume 424, pages 205–209 (2003)Cite this article

Abstract

Paired-associate learning is often used to examine episodic memory in humans1. Animal models include the recall of food-cache locations by scrub jays2 and sequential memory3,4. Here we report a model in which rats encode, during successive sample trials, two paired associates (flavours of food and their spatial locations) and display better-than-chance recall of one item when cued by the other. In a first study, pairings of a particular foodstuff and its location were never repeated, so ensuring unique ‘what–where’ attributes. Blocking _N_-methyl-d-aspartate receptors in the hippocampus—crucial for the induction of certain forms of activity-dependent synaptic plasticity5,6—impaired memory encoding but had no effect on recall. Inactivating hippocampal neural activity by blocking α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors impaired both encoding and recall. In a second study, two paired associates were trained repeatedly over 8 weeks in new pairs, but blocking of hippocampal AMPA receptors did not affect their recall. Thus we conclude that unique what–where paired associates depend on encoding and retrieval within a hippocampal memory space7,8, with consolidation of the memory traces representing repeated paired associates in circuits elsewhere.

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Acknowledgements

We thank N. Clayton, D. Donaldson, P. Dudchenko, L. Jacobs, E. Moser and E. Wood for discussion. Funded by MRC Innovation and Programme Grants and an E.U. Framework V Grant.

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Author notes

  1. R. G. M. Morris
    Present address: GlaxoSmithKline, Centre for Excellence in Drug Discovery, Harlow, Essex, CM19 5AW, UK

Authors and Affiliations

  1. Laboratory for Cognitive Neuroscience, Division and Centre for Neuroscience, The University of Edinburgh, 1 George Square, EH8 9JZ, Edinburgh, UK
    R. Langston & R. G. M. Morris
  2. GlaxoSmithKline, Centre for Excellence in Drug Discovery, Harlow, Essex, CM19 5AW, UK
    M. Day

Authors

  1. M. Day
  2. R. Langston
  3. R. G. M. Morris

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Correspondence toR. G. M. Morris.

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The authors declare that they have no competing financial interests.

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Day, M., Langston, R. & Morris, R. Glutamate-receptor-mediated encoding and retrieval of paired-associate learning.Nature 424, 205–209 (2003). https://doi.org/10.1038/nature01769

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