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

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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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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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