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Reversible neural inactivation reveals hippocampal participation in several memory processes

Nature Neuroscience volume 2, pages 898–905 (1999)Cite this article

Abstract

Studies of patients and animals with brain lesions have implicated the hippocampal formation in spatial, declarative/relational and episodic types of memory. These and other types of memory consist of a series of interdependent but potentially dissociable memory processes—encoding, storage, consolidation and retrieval. To identify whether hippocampal activity contributes to these processes independently, we used a novel method of inactivating synaptic transmission using a water-soluble antagonist of AMPA/kainate glutamate receptors. Once calibrated using electrophysiological and two-deoxyglucose techniques in vivo, drug or vehicle was infused chronically or acutely into the dorsal hippocampus of rats at appropriate times during or after training in a water maze. Our findings indicate that hippocampal neural activity is necessary for both encoding and retrieval of spatial memory and for either trace consolidation or long-term storage.

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Figure 1: The AMPA/kainate receptor antagonist LY326325 blocks fast synaptic transmission at perforant path/granule cell synapses.
Figure 2: The AMPA/kainate receptor antagonist LY326325 reduces glucose utilization in the dorsal hippocampus.
Figure 3: Hippocampal inactivation disrupts encoding- and retrieval-related processes of spatial memory.
Figure 4: Chronic but not acute inactivation of the dorsal hippocampus interferes with a post-training memory process.
Figure 5: Chronic LY interferes with a post-training memory process but does not cause any residual impairment of encoding or retrieval.
Figure 6: The specificity of the effects of post-training hippocampal inactivation.

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Acknowledgements

This work was supported by an MRC Programme Grant to R.G.M.M., by grants from CNRS, The Royal Society and Fondation Cino del Duca to J.M. and by a Wellcome Trust grant to J.McC. We are grateful to Darryl Schoepp of Lilly USA for supplying LY326325 and to Jane Knox and Patrick Spooner for technical support.

Author information

Author notes

  1. H. Bridge

    Present address: Department of Experimental Psychology, University of Oxford, Oxford, OX1 3UD, UK

  2. G. Riedel and J. Micheau: The first two authors contributed equally to this work.

Authors and Affiliations

  1. Department and Centre for Neuroscience, University of Edinburgh Medical School, Crichton Street, Edinburgh, EH8 9LE, UK

    G. Riedel, E.v.L. Roloff, S.J. Martin, H. Bridge, L. de Hoz, B. Poeschel & R.G.M. Morris

  2. Department of Biomedical Sciences, University of Aberdeen, Aberdeen, AB25 2ZD, UK

    G. Riedel & E.v.L. Roloff

  3. Laboratoire de Neurosciences Comportementales et Cognitives, CNRS UMR 5807, Université de Bordeaux I, Avenue des Facultés, Talence Cedex, 33405, France

    J. Micheau

  4. Department of Neuroscience, Wellcome Surgical Institute University of Glasgow, Garscube Estate, Glasgow, G61 1QH, UK

    A.G.M. Lam & J. McCulloch

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Riedel, G., Micheau, J., Lam, A. et al. Reversible neural inactivation reveals hippocampal participation in several memory processes. Nat Neurosci 2, 898–905 (1999). https://doi.org/10.1038/13202

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