title: Interaction between αCaMKII and GluN2B controls ERK-dependent plasticity.
abstract: Understanding how brief synaptic events can lead to sustained changes in synaptic structure and strength is a necessary step in solving the rules governing learning and memory. Activation of ERK1/2 (extracellular signal regulated protein kinase 1/2) plays a key role in the control of functional and structural synaptic plasticity. One of the triggering events that activates ERK1/2 cascade is an NMDA receptor (NMDAR)-dependent rise in free intracellular Ca(2+) concentration. However the mechanism by which a short-lasting rise in Ca(2+) concentration is transduced into long-lasting ERK1/2-dependent plasticity remains unknown. Here we demonstrate that although synaptic activation in mouse cultured cortical neurons induces intracellular Ca(2+) elevation via both GluN2A and GluN2B-containing NMDARs, only GluN2B-containing NMDAR activation leads to a long-lasting ERK1/2 phosphorylation. We show that αCaMKII, but not βCaMKII, is critically involved in this GluN2B-dependent activation of ERK1/2 signaling, through a direct interaction between GluN2B and αCaMKII. We then show that interfering with GluN2B/αCaMKII interaction prevents synaptic activity from inducing ERK-dependent increases in synaptic AMPA receptors and spine volume. Thus, in a developing circuit model, the brief activity of synaptic GluN2B-containing receptors and the interaction between GluN2B and αCaMKII have a role in long-term plasticity via the control of ERK1/2 signaling. Our findings suggest that the roles that these major molecular elements have in learning and memory may operate through a common pathway.
authors.affiliation: Université de Caen-Basse Normandie, CNRS UMR 6232, CINAPS-PSY, 14 000 Caen, France.
authors.forename: Farida
authors.initials: F
authors.lastname: El Gaamouch
authors.forename: Alain
authors.initials: A
authors.lastname: Buisson
authors.forename: Olivier
authors.initials: O
authors.lastname: Moustié
authors.forename: Mado
authors.initials: M
authors.lastname: Lemieux
authors.forename: Simon
authors.initials: S
authors.lastname: Labrecque
authors.forename: Bruno
authors.initials: B
authors.lastname: Bontempi
authors.forename: Paul
authors.initials: P
authors.lastname: De Koninck
authors.forename: Olivier
authors.initials: O
authors.lastname: Nicole
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D049229:Dendritic Spines / Q000378:metabolism; D000076122:Disks Large Homolog 4 Protein; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D051528:Guanylate Kinases / Q000378:metabolism; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000502:physiology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D038761:Photobleaching; D026902:Potassium Channel Blockers / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D058787:GABA-A Receptor Antagonists; D008164:Luminescent Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C121001:NR2B NMDA receptor; D026902:Potassium Channel Blockers; D034741:RNA, Small Interfering; D016194:Receptors, N-Methyl-D-Aspartate; D015761:4-Aminopyridine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D051528:Guanylate Kinases; D002118:Calcium; D001640:Bicuculline