title: Formation of GABAAreceptor complexes containing α1 and α5 subunits is paralleling a multiple T-maze learning task in mice.
abstract: There is limited information on the role of GABA type A receptors (GABAARs) containing α1, α5 and γ2 subunits in learning and memory. Here, we assessed the possible role of such receptors in spatial learning using the multiple T-maze (MTM) paradigm. C57BL/6J mice were trained in the MTM which induced elevated levels of α1 and α5 subunit-containing hippocampal GABAAR complexes. Moreover, spatial learning evoked a significant increase in the colocalization of α1 and α5 subunits in both, CA1 and dentate gyrus regions of the hippocampus suggesting the formation of complexes containing both subunits. Additionally, the presence of α1, α5 and γ2 subunits in high molecular weight GABAARs was detected and significant correlation in the level of α1-containing complexes with those containing α5 and γ2 subunits was demonstrated. Accordingly, α1 deficiency led to decreased levels of γ2 subunit-containing complexes, however, had no effect on α5-containing ones. On the other hand, α1 knockout mice showed impaired performance in the MTM correlating with increased levels of α5 subunit-containing GABAARs in comparison to trained floxed control animals which quickly learned the task. Taken together, these results suggest that α1, α5 and γ2-containing hippocampal GABAAR complexes play an essential role in spatial learning and memory in which targeted disruption of the α1 subunit produces profound deficits.
authors.affiliation: Department of Pediatrics, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors.forename: Maryam
authors.initials: M
authors.lastname: Ghafari
authors.affiliation: Department of Pediatrics, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors.forename: Soheil Keihan
authors.initials: SK
authors.lastname: Falsafi
authors.affiliation: Department of Pediatrics, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.|Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090, Vienna, Austria.
authors.forename: Edit
authors.initials: E
authors.lastname: Szodorai
authors.affiliation: Department of Pediatrics, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria.
authors.forename: Lin
authors.initials: L
authors.lastname: Li
authors.affiliation: Core Unit of Biomedical Research, Division of Laboratory Animal Science and Genetics, Medical University of Vienna, Brauhausgasse 34, 2325, Himberg, Austria.
authors.forename: Harald
authors.initials: H
authors.lastname: Höger
authors.affiliation: Department of Pathobiology of the Nervous System, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090, Vienna, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Berger
authors.affiliation: Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090, Vienna, Austria.
authors.forename: Karoline
authors.initials: K
authors.lastname: Fuchs
authors.affiliation: Department of Molecular Neurosciences, Center for Brain Research, Medical University of Vienna, Spitalgasse 4, 1090, Vienna, Austria.
authors.forename: Werner
authors.initials: W
authors.lastname: Sieghart
authors.affiliation: Department of Pharmaceutical Chemistry, University of Vienna, Althanstrasse 14/2F346, 1090, Vienna, Austria. gert.lubec@univie.ac.at.
authors.forename: Gert
authors.initials: G
authors.lastname: Lubec
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology*; D008297:Male; D018782:Maze Learning / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
chemical_list: D021122:Protein Subunits; D011963:Receptors, GABA-A
keywords: BN-PAGE; GABAA receptor complexes; GABAAR α1 KO mice; Mass spectrometry; Multiple T-maze; Spatial memory