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Restoration of spatial working memory by genetic rescue of GluR-A–deficient mice

Nature Neuroscience volume 8, pages 270–272 (2005)Cite this article

Abstract

Gene-targeted mice lacking the AMPA receptor subunit GluR-A (also called GluR1 encoded by the gene Gria1,) have deficits in hippocampal CA3–CA1 long-term potentiation (LTP) and have profoundly impaired hippocampus-dependent spatial working memory (SWM) tasks, although their spatial reference memory remains normal. Here we show that forebrain-localized expression of GFP-tagged GluR-A subunits in GluR-A–deficient mice rescues SWM, paralleling its rescue of CA3–CA1 LTP. This provides powerful new evidence linking hippocampal GluR-A–dependent synaptic plasticity to rapid, flexible memory processing.

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Figure 1: GFP-tagged GluR-A expression rescues spatial working memory performance in GluR-A–deficient mice.
Figure 2: Immunohistochemical comparison of β-gal expression in dorsal and ventral hippocampal CA1 and CA3 of GluR-A–deficient mice expressing GFP–GluR-A.

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Acknowledgements

This work was supported by the Wellcome Trust (65298 and 074385), by a European Union Framework V grant (QLG3-CT-1999-01022) awarded to P.H.S., R.S. and J.N.P.R. and by Deutsche Forschungsgemeinschaft grants to R.S. (SP602/1 and SFB633/4).

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Authors and Affiliations

  1. Department of Experimental Psychology, University of Oxford, South Parks Road, Oxford, OX1 3UD, UK

    W B Schmitt, R M J Deacon, J N P Rawlins & D M Bannerman

  2. Department of Molecular Neurobiology, Max-Planck-Institute of Medical Research, Heidelberg, D-69120, Jahnstrasse 29, Germany

    R Sprengel, V Mack, R W Draft & P H Seeburg

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  1. W B Schmitt
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  2. R Sprengel
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  3. V Mack
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  4. R W Draft
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  6. R M J Deacon
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  7. J N P Rawlins
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  8. D M Bannerman
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Correspondence to D M Bannerman.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Fig. 1

Percentage of cells expressing αCaMKII/tTA–driven, nuclear-localized β-galactosidase in CA1 subfield of dorsal and ventral hippocampus for each of the five animals assessed. (PDF 175 kb)

Supplementary Table 1

Effects of the GluR-A AMPA receptor subunit knockout mutation and its subsequent forebrain-specific rescue on tests of emotionality, locomotor activity, motor coordination and species-typical behaviors. (PDF 29 kb)

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Schmitt, W., Sprengel, R., Mack, V. et al. Restoration of spatial working memory by genetic rescue of GluR-A–deficient mice. Nat Neurosci 8, 270–272 (2005). https://doi.org/10.1038/nn1412

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