title: NMDA receptor subunit NR2A is required for rapidly acquired spatial working memory but not incremental spatial reference memory.
abstract: NMDA receptors (NMDARs) containing NR2A (epsilon1) subunits are key contributors to hippocampal long-term potentiation (LTP) induction in adult animals and have therefore been widely implicated in hippocampus-dependent spatial learning. Here we show that mice lacking the NR2A subunit or its C-terminal intracellular domain exhibit impaired spatial working memory (SWM) but normal spatial reference memory (SRM). Both NR2A mutants acquired the SRM version of the water maze task, and the SRM component of the radial maze, as well as controls. They were, however, impaired on a non-matching-to-place T-maze task, and on the SWM component of the radial maze. In addition, NR2A knock-out mice displayed a diminished spatial novelty preference in a spontaneous exploration Y-maze task, and were impaired on a T-maze task in which distinctive inserts present on the floor of the maze determined which goal arm contained the reward, but only if there was a discontiguity between the conditional cue and the place at which the reward was delivered. This dissociation of spatial memory into distinctive components is strikingly similar to results obtained with mice lacking glutamate receptor-A (GluR-A)-containing AMPA receptors, which support long-term potentiation expression. These results identify a specific role for a NMDAR-dependent signaling pathway that leads to the activation of a GluR-A-dependent expression mechanism in a rapidly acquired, flexible form of spatial memory. This mechanism depends on the C-terminal intracellular domain of the NR2A subunit. In contrast, the ability to associate a particular spatial location with the water maze escape platform or food reward is NR2A independent, as well as GluR-A independent.
authors.affiliation: Department of Experimental Psychology, University of Oxford, Oxford OX1 3UD, United Kingdom. david.bannerman@psy.ox.ac.uk
authors.forename: David M
authors.initials: DM
authors.lastname: Bannerman
authors.forename: Burkhard
authors.initials: B
authors.lastname: Niewoehner
authors.forename: Louisa
authors.initials: L
authors.lastname: Lyon
authors.forename: Carola
authors.initials: C
authors.lastname: Romberg
authors.forename: Wolfram B
authors.initials: WB
authors.lastname: Schmitt
authors.forename: Amy
authors.initials: A
authors.lastname: Taylor
authors.forename: David J
authors.initials: DJ
authors.lastname: Sanderson
authors.forename: James
authors.initials: J
authors.lastname: Cottam
authors.forename: Rolf
authors.initials: R
authors.lastname: Sprengel
authors.forename: Peter H
authors.initials: PH
authors.lastname: Seeburg
authors.forename: Georg
authors.initials: G
authors.lastname: Köhr
authors.forename: John N P
authors.initials: JN
authors.lastname: Rawlins
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D003213:Conditioning, Psychological / Q000502:physiology; D005106:Exploratory Behavior / Q000502:physiology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008570:Memory, Short-Term / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000172:deficiency / Q000502:physiology*; D013028:Space Perception / Q000502:physiology*; D013997:Time Factors
chemical_list: C120997:NR2A NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate