title: Enhanced learning and memory and altered GABAergic synaptic transmission in mice lacking the alpha 5 subunit of the GABAA receptor.
abstract: The alpha5 subunit of the GABA(A) receptor is localized mainly to the hippocampus of the mammalian brain. The significance of this rather distinct localization and the function of alpha5-containing GABA(A) receptors has been explored by targeted disruption of the alpha5 gene in mice. The alpha5 -/- mice showed a significantly improved performance in a water maze model of spatial learning, whereas the performance in non-hippocampal-dependent learning and in anxiety tasks were unaltered in comparison with wild-type controls. In the CA1 region of hippocampal brain slices from alpha5 -/- mice, the amplitude of the IPSCs was decreased, and paired-pulse facilitation of field EPSP (fEPSP) amplitudes was enhanced. These data suggest that alpha5-containing GABA(A) receptors play a key role in cognitive processes by controlling a component of synaptic transmission in the CA1 region of the hippocampus.
authors.affiliation: Neuroscience Research Center, Merck Sharp and Dohme Research Laboratories, Harlow, Essex, CM20 2QR, United Kingdom.
authors.forename: Neil
authors.initials: N
authors.lastname: Collinson
authors.forename: Frederick M
authors.initials: FM
authors.lastname: Kuenzi
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Jarolimek
authors.forename: Karen A
authors.initials: KA
authors.lastname: Maubach
authors.forename: Rosa
authors.initials: R
authors.lastname: Cothliff
authors.forename: Cyrille
authors.initials: C
authors.lastname: Sur
authors.forename: Alison
authors.initials: A
authors.lastname: Smith
authors.forename: Franklin M
authors.initials: FM
authors.lastname: Otu
authors.forename: Owain
authors.initials: O
authors.lastname: Howell
authors.forename: John R
authors.initials: JR
authors.lastname: Atack
authors.forename: Ruth M
authors.initials: RM
authors.lastname: McKernan
authors.forename: Guy R
authors.initials: GR
authors.lastname: Seabrook
authors.forename: Gerry R
authors.initials: GR
authors.lastname: Dawson
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Whiting
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Rosahl
mesh_terms: D000818:Animals; D001362:Avoidance Learning; D001522:Behavior, Animal; D004553:Electric Conductivity; D019706:Excitatory Postsynaptic Potentials; D005260:Female; D006624:Hippocampus / Q000502:physiology*; D007700:Kinetics; D007858:Learning; D017774:Long-Term Potentiation; D008297:Male; D018782:Maze Learning; D008568:Memory; D051379:Mice; D018345:Mice, Knockout; D021122:Protein Subunits; D011963:Receptors, GABA-A / Q000235:genetics / Q000502:physiology*; D009435:Synaptic Transmission; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D021122:Protein Subunits; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid