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.