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 (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 (Gria1^Hpc 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, Gria1^Hpc 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.