title: Forebrain-specific glutamate receptor B deletion impairs spatial memory but not hippocampal field long-term potentiation.
abstract: We demonstrate the fundamental importance of glutamate receptor B (GluR-B) containing AMPA receptors in hippocampal function by analyzing mice with conditional GluR-B deficiency in postnatal forebrain principal neurons (GluR-B(deltaFb)). These mice are as adults sufficiently robust to permit comparative cellular, physiological, and behavioral studies. GluR-B loss induced moderate long-term changes in the hippocampus of GluR-B(deltaFb) mice. Parvalbumin-expressing interneurons in the dentate gyrus and the pyramidal cells in CA3 were decreased in number, and neurogenesis in the subgranular zone was diminished. Excitatory synaptic CA3-to-CA1 transmission was reduced, although synaptic excitability, as quantified by the lowered threshold for population spike initiation, was increased compared with control mice. These changes did not alter CA3-to-CA1 long-term potentiation (LTP), which in magnitude was similar to LTP in control mice. The altered hippocampal circuitry, however, affected spatial learning in GluR-B(deltaFb) mice. The primary source for the observed changes is most likely the AMPA receptor-mediated Ca2+ signaling that appears after GluR-B depletion, because we observed similar alterations in GluR-B(QFb) mice in which the expression of Ca2+-permeable AMPA receptors in principal neurons was induced by postnatal activation of a Q/R-site editing-deficient GluR-B allele.
authors.affiliation: Department of Molecular Neurobiology, Max Planck Institute for Medical Research, D-69120 Heidelberg, Germany.
authors.forename: Derya R
authors.initials: DR
authors.lastname: Shimshek
authors.forename: Vidar
authors.initials: V
authors.lastname: Jensen
authors.forename: Tansu
authors.initials: T
authors.lastname: Celikel
authors.forename: Yu
authors.initials: Y
authors.lastname: Geng
authors.forename: Bettina
authors.initials: B
authors.lastname: Schupp
authors.forename: Thorsten
authors.initials: T
authors.lastname: Bus
authors.forename: Volker
authors.initials: V
authors.lastname: Mack
authors.forename: Verena
authors.initials: V
authors.lastname: Marx
authors.forename: Øivind
authors.initials: Ø
authors.lastname: Hvalby
authors.forename: Peter H
authors.initials: PH
authors.lastname: Seeburg
authors.forename: Rolf
authors.initials: R
authors.lastname: Sprengel
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002455:Cell Division; D018891:Dentate Gyrus / Q000166:cytology / Q000378:metabolism; D005106:Exploratory Behavior; D020868:Gene Silencing; D006624:Hippocampus / Q000166:cytology / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D016548:Prosencephalon / Q000378:metabolism*; D018091:Receptors, AMPA / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013028:Space Perception / Q000502:physiology*; D009435:Synaptic Transmission
chemical_list: D018091:Receptors, AMPA; C115953:glutamate receptor type B; D002118:Calcium