Journal
JOURNAL OF NEUROSCIENCE
Volume 32, Issue 31, Pages 10767-10779Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.5622-11.2012
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Funding
- French Ministry of Research
- Agence National de la Recherche [ANR MALZ 2010-001-02]
- Regional Council of Basse-Normandie France
- Canadian Institutes of Health Research (CIHR)
- Natural Science and Engineering Research Council of Canada (NSERC)
- CIHR
- Fond de la Recherche en Sante du Quebec
- CIHR Neurophysics training grant
- Alzheimer Foundation
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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 Ca2+ concentration. However the mechanism by which a short-lasting rise in Ca2+ 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 Ca2+ elevation via both GluN2A and GluN2B-containing NMDARs, only GluN2B-containing NMDAR activation leads to a long-lasting ERK1/2 phosphorylation. We show that alpha CaMKII, but not beta CaMKII, is critically involved in this GluN2B-dependent activation of ERK1/2 signaling, through a direct interaction between GluN2B and alpha CaMKII. We then show that interfering with GluN2B/alpha CaMKII 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 alpha CaMKII 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.
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