title: CaMKII binding to GluN2B is important for massed spatial learning in the Morris water maze.
abstract: Learning and memory as well as long-term potentiation (LTP) depend on Ca (2+) influx through the NMDA-type glutamate receptor (NMDAR) and the resulting activation of the Ca (2+) and calmodulin-dependent protein kinase (CaMKII). Ca (2+) influx via the NMDAR triggers CaMKII binding to the NMDAR for enhanced CaMKII accumulation at post-synaptic sites that experience heightened activity as occurring during LTP. Previously, we generated knock-in (KI) mice in which we replaced two residues in the NMDAR GluN2B subunit to impair CaMKII binding to GluN2B. Various forms of LTP at the Schaffer collateral synapses in CA1 are reduced by 50%. Nevertheless, working memory in the win-shift 8 arm maze and learning of the Morris water maze (MWM) task was normal in the KI mice although recall of the task was impaired in these mice during the period of early memory consolidation. We now show that massed training in the MWM task within a single day resulted in impaired learning. However, learning and recall of the Barnes maze task and contextual fear conditioning over one or multiple days were surprisingly unaffected. The differences observed in the MWM compared to the Barnes maze and contextual fear conditioning suggest a differential involvement of CaMKII and the specific interaction with GluN2B, probably depending on varying degrees of stress, cognitive demand or even potentially different plasticity mechanisms associated with the diverse tasks.
authors.affiliation: Department of Pharmacology, School of Medicine, University of California, Davis, 95616-8636, USA.
authors.forename: Ivar S
authors.initials: IS
authors.lastname: Stein
authors.affiliation: Department of Pharmacology, School of Medicine, University of California, Davis, 95616-8636, USA.
authors.forename: Michaela S
authors.initials: MS
authors.lastname: Donaldson
authors.affiliation: Department of Pharmacology, School of Medicine, University of California, Davis, 95616-8636, USA.
authors.forename: Johannes W
authors.initials: JW
authors.lastname: Hell