title: Hippocampal GluA1 expression in Gria1-/-mice only partially restores spatial memory performance deficits.
abstract: 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 (Gria1Hpcmice) 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, Gria1Hpcmice 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.
authors.affiliation: Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Heinrich-Hoffmann-Straße 10, 60528 Frankfurt am Main, Germany; Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany. Electronic address: florian.freudenberg@kgu.de.
authors.forename: Florian
authors.initials: F
authors.lastname: Freudenberg
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany.
authors.forename: Evgeny
authors.initials: E
authors.lastname: Resnik
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kolleker
authors.affiliation: Department of Neurophysiology, Donders Center for Neuroscience, Radboud University Nijmegen, P.O. Box 9010, Mailbox 33, 6500 AA Nijmegen, The Netherlands.
authors.forename: Tansu
authors.initials: T
authors.lastname: Celikel
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany; Max Planck Research Group at the Institute for Anatomy and Cell Biology, Heidelberg University, Im Neuenheimer Feld 307, 69120 Heidelberg, Germany.
authors.forename: Rolf
authors.initials: R
authors.lastname: Sprengel
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Jahnstrasse 29, 69120 Heidelberg, Germany.
authors.forename: Peter H
authors.initials: PH
authors.lastname: Seeburg
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D018014:Gene Transfer Techniques; D006624:Hippocampus / Q000378:metabolism*; D008569:Memory Disorders / Q000378:metabolism* / Q000503:physiopathology*; D008570:Memory, Short-Term / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000172:deficiency / Q000378:metabolism*; D065852:Spatial Memory / Q000502:physiology*
chemical_list: D018091:Receptors, AMPA
keywords: Adeno-associated virus; GluR-A; GluR1; Mouse; Viral gene transfer