Search form

TitleInteraction between αCaMKII and GluN2B controls ERK-dependent plasticity.
Publication TypeJournal Article
Year of Publication2012
AuthorsGaamouch, Farida El, Alain Buisson, Olivier Moustié, Mado Lemieux, Simon Labrecque, Bruno Bontempi, Paul De Koninck, and Olivier Nicole
JournalJ Neurosci
Volume32
Issue31
Pagination10767-79
Date Published2012 Aug 1
ISSN1529-2401
Keywords4-Aminopyridine, Analysis of Variance, Animals, Bicuculline, Calcium, Calcium-Calmodulin-Dependent Protein Kinase Type 2, Cells, Cultured, Cerebral Cortex, Dendritic Spines, Enzyme Inhibitors, Excitatory Amino Acid Antagonists, GABA-A Receptor Antagonists, Guanylate Kinase, Immunoprecipitation, In Vitro Techniques, Luminescent Proteins, Male, MAP Kinase Signaling System, Membrane Proteins, Mice, Mice, Inbred C57BL, Microtubule-Associated Proteins, Neuronal Plasticity, Neurons, Phosphorylation, Photobleaching, Potassium Channel Blockers, Rats, Receptors, N-Methyl-D-Aspartate, RNA, Small Interfering, Transfection
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.

DOI10.1523/JNEUROSCI.5622-11.2012
Alternate JournalJ. Neurosci.
PubMed ID22855824
Grant List / / Canadian Institutes of Health Research / Canada