title: CaMKII binding to GluN2B is critical during memory consolidation.
abstract: Memory is essential for our normal daily lives and our sense of self. Ca(2+) influx through the NMDA-type glutamate receptor (NMDAR) and the ensuing activation of the Ca(2+) and calmodulin-dependent protein kinase (CaMKII) are required for memory formation and its physiological correlate, long-term potentiation (LTP). The Ca(2+) influx induces CaMKII binding to the NMDAR to strategically recruit CaMKII to synapses that are undergoing potentiation. We generated mice with two point mutations that impair CaMKII binding to the NMDAR GluN2B subunit. Ca(2+)-triggered postsynaptic accumulation is largely abrogated for CaMKII and destabilized for TARPs, which anchor AMPA-type glutamate receptors (AMPAR). LTP is reduced by 50% and phosphorylation of the AMPAR GluA1 subunit by CaMKII, which enhances AMPAR conductance, impaired. The mutant mice learn the Morris water maze (MWM) as well as WT but show deficiency in recall during the period of early memory consolidation. Accordingly, the activity-driven interaction of CaMKII with the NMDAR is important for recall of MWM memory as early as 24 h, but not 1-2 h, after training potentially due to impaired consolidation.
authors.affiliation: Department of Pharmacology, Roy J and Lucille A Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
authors.forename: Amy R
authors.initials: AR
authors.lastname: Halt
authors.forename: Robert F
authors.initials: RF
authors.lastname: Dallapiazza
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.forename: Ivar S
authors.initials: IS
authors.lastname: Stein
authors.forename: Hai
authors.initials: H
authors.lastname: Qian
authors.forename: Scott
authors.initials: S
authors.lastname: Juntti
authors.forename: Sonja
authors.initials: S
authors.lastname: Wojcik
authors.forename: Nils
authors.initials: N
authors.lastname: Brose
authors.forename: Alcino J
authors.initials: AJ
authors.lastname: Silva
authors.forename: Johannes W
authors.initials: JW
authors.lastname: Hell
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D008568:Memory; D051379:Mice; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D020125:Mutation, Missense; D017354:Point Mutation; D011485:Protein Binding; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*
chemical_list: D050505:Mutant Proteins; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2