title: Contribution of hippocampal and extra-hippocampal NR2B-containing NMDA receptors to performance on spatial learning tasks.
abstract: Controversy revolves around the differential contribution of NR2A- and NR2B-containing NMDA receptors, which coexist in principal forebrain neurons, to synaptic plasticity and learning in the adult brain. Here, we report genetically modified mice in which the NR2B subunit is selectively ablated in principal neurons of the entire postnatal forebrain or only the hippocampus. NR2B ablation resulted in smaller NMDA receptor-mediated EPSCs with accelerated decay kinetics, as recorded in CA1 pyramidal cells. CA3-to-CA1 field LTP remained largely unaltered, although a pairing protocol revealed decreased NMDA receptor-mediated charge transfer and reduced cellular LTP. Mice lacking NR2B in the forebrain were impaired on a range of memory tasks, presenting both spatial and nonspatial phenotypes. In contrast, hippocampus-specific NR2B ablation spared hippocampus-dependent, hidden-platform water maze performance but induced a selective, short-term, spatial working memory deficit for recently visited places. Thus, both hippocampal and extra-hippocampal NR2B containing NMDA receptors critically contribute to spatial performance.
authors.affiliation: Department of Clinical Neurobiology, University of Heidelberg, D-69120 Heidelberg, Germany.
authors.forename: Jakob
authors.initials: J
authors.lastname: von Engelhardt
authors.forename: Beril
authors.initials: B
authors.lastname: Doganci
authors.forename: Vidar
authors.initials: V
authors.lastname: Jensen
authors.forename: Øivind
authors.initials: Ø
authors.lastname: Hvalby
authors.forename: Christina
authors.initials: C
authors.lastname: Göngrich
authors.forename: Amy
authors.initials: A
authors.lastname: Taylor
authors.forename: Chris
authors.initials: C
authors.lastname: Barkus
authors.forename: David J
authors.initials: DJ
authors.lastname: Sanderson
authors.forename: J Nicholas P
authors.initials: JN
authors.lastname: Rawlins
authors.forename: Peter H
authors.initials: PH
authors.lastname: Seeburg
authors.forename: David M
authors.initials: DM
authors.lastname: Bannerman
authors.forename: Hannah
authors.initials: H
authors.lastname: Monyer
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D004192:Discrimination, Psychological / Q000502:physiology; D004558:Electric Stimulation / Q000379:methods; D003576:Electron Transport Complex IV / Q000378:metabolism; D005071:Evoked Potentials / Q000502:physiology; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D005106:Exploratory Behavior / Q000187:drug effects / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009154:Mutation; D009474:Neurons / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D010775:Photic Stimulation / Q000379:methods; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000502:physiology*; D021641:Recognition, Psychology / Q000502:physiology; D013028:Space Perception / Q000187:drug effects / Q000502:physiology
chemical_list: D018683:Excitatory Amino Acid Agents; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D003576:Electron Transport Complex IV