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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References
Tulving, E. Elements of Episodic Memory (Oxford Univ. Press, New York, 1983)
Clayton, N. S. & Dickinson, A. Episodic-like memory during cache recovery by scrub jays. Nature 395, 272–274 (1998)
Fortin, N. J., Agster, K. L. & Eichenbaum, H. B. Critical role of the hippocampus in memory for sequences of events. Nature Neurosci. 5, 458–462 (2002)
Kesner, R. P., Gilbert, P. E. & Barua, L. A. The role of the hippocampus in memory for the temporal order of a sequence of odors. Behav. Neurosci. 116, 286–290 (2002)
Bliss, T. V. P. & Lømo, T. Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J. Physiol. (Lond.) 232, 331–356 (1973)
Martin, S. J., Grimwood, P. D. & Morris, R. G. M. Synaptic plasticity and memory: An evaluation of the hypothesis. Annu. Rev. Neurosci. 23, 649–711 (2000)
Morris, R. G. M. & Frey, U. Hippocampal synaptic plasticity: Role in spatial learning or the automatic recording of attended experience? Phil. Trans. R. Soc. Lond. B 352, 1489–1503 (1997)
Eichenbaum, H., Dudchenko, P. A., Wood, E. R., Shapiro, M. & Tanila, H. The hippocampus, memory and place cells: Is it a spatial memory or a memory space? Neuron 23, 209–226 (1999)
Bleakman, D. & Lodge, D. Neuropharmacology of AMPA and kainate receptors. Neuropharmacology 37, 1187–1204 (1998)
Bliss, T. V. & Collingridge, G. L. A synaptic model of memory: Long-term potentiation in the hippocampus. Nature 361, 31–39 (1993)
Cowan, W. M., Sudhof, T. C. & Stevens, C. F. Synapses (Johns Hopkins Univ. Press, 2001)
O'Keefe, J. & Nadel, L. The Hippocampus as a Cognitive Map (Clarendon Press, Oxford, 1978)
Gilbert, P. E. & Kesner, R. P. Role of the rodent hippocampus in paired-associate learning involving associations between a stimulus and a spatial location. Behav. Neurosci. 116, 63–71 (2002)
Steele, R. J. & Morris, R. G. M. Delay-dependent impairment of a matching-to-place task with chronic and intrahippocampal infusion of the NMDA-antagonist d-AP5. Hippocampus 9, 118–136 (1999)
Kim, J. J. & Fanselow, M. S. Modality-specific retrograde amnesia of fear. Science 256, 675–677 (1992)
Sakai, K. & Miyashita, Y. Neural organization for the long-term memory of paired associates. Nature 354, 152–155 (1991)
Gaffan, D. Scene-specific memory for objects: A model of episodic memory impairment in monkeys with fornix transection. J. Cogn. Neurosci. 6, 305–320 (1994)
Mishkin, M. & Delacour, J. An analysis of short-term visual memory in the monkey. J. Exp. Psychol.: Anim. Behav. Processes 1, 326–334 (1975)
Zola-Morgan, S. & Squire, L. R. Medial temporal lesions in monkeys impair memory on a variety of tasks sensitive to human amnesia. Behav. Neurosci. 99, 22–34 (1985)
Brun, V. H. et al. Place cells and place recognition maintained by direct entorhinal–hippocampal circuitry. Science 296, 2243–2246 (2002)
Zeineh, M. M., Engel, S. A., Thompson, P. M. & Bookheimer, S. Y. Dynamics of the Hippocampus during encoding and retrieval of face–name pairs. Science 299, 577–580 (2003)
Takahashi, T., Svoboda, K. & Malinow, R. Experience strengthening transmission by driving AMPA receptors into synapses. Science 299, 1585–1588 (2003)
Gardiner, J. M. in Episodic Memory: New Directions in Research (eds Baddeley, A., Conway, M. & Aggleton, J.) 11–30 (Oxford Univ. Press, 2001)
Swainson, R. et al. Early detection and differential diagnosis of Alzheimer's disease and depression with neuropsychological tasks. Dement. Geriatr. Cogn. Disord. 12, 265–280 (2001)
Lisman, J. E. Relating hippocampal circuitry to function: Recall of memory sequences by reciprocal dentate–CA3 interactions. Neuron 22, 233–242 (1999)
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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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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DOI: https://doi.org/10.1038/nature01769
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