Hippocampal GluA1 expression in Gria1−/− mice only partially restores spatial memory performance deficits

Spatial working memory (SWM) is an essential cognitive function important for survival in a competitive environment. In rodents SWM requires an intact hippocampus and SWM expression is impaired in mice lacking the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluA1 (Gr...

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Main Authors: Freudenberg, Florian (Author) , Resnik, Evgeny (Author) , Kolleker, Alexander (Author) , Celikel, Tansu (Author) , Sprengel, Rolf (Author) , Seeburg, Peter H. (Author)
Format: Article (Journal) Editorial
Language:English
Published: 11 July 2016
In: Neurobiology of learning and memory
Year: 2016, Volume: 135, Pages: 83-90
ISSN:1095-9564
DOI:10.1016/j.nlm.2016.07.005
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Author Notes:Florian Freudenberg, Evgeny Resnik, Alexander Kolleker, Tansu Celikel, Rolf Sprengel, Peter H. Seeburg
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Summary:Spatial working memory (SWM) is an essential cognitive function important for survival in a competitive environment. In rodents SWM requires an intact hippocampus and SWM expression is impaired in mice lacking the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluA1 (Gria1−/− mice). Here we used viral gene transfer to show that re-expression of GluA1 in the hippocampus can affect the behavioral performance of GluA1 deficient mice. We found that Gria1−/− mice with hippocampus-specific rescue of GluA1 expression (Gria1Hpc mice) are more anxious, less hyperactive and only partly impaired in SWM expression in the Y-maze spatial novelty preference paradigm compared to Gria1−/− mice. However, Gria1Hpc mice still express SWM performance deficits when tested in the rewarded alternation T-maze task. Thus, the restoration of hippocampal function affects several behaviors of GluA1 deficient mice - including SWM expression - in different tasks. The virus-mediated GluA1 expression in Gria1−/− mice is not sufficient for a comprehensive SWM restoration, suggesting that both hippocampal as well as extra-hippocampal GluA1-containing AMPA receptors contribute to SWM.
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ISSN:1095-9564
DOI:10.1016/j.nlm.2016.07.005