CaMKII: A Master Functional and Structural Molecule in Synaptic Plasticity and Memory

  • Magdalena SanhuezaEmail author
  • German Fernandez


Learning and memory relies, at least in part, on activity-dependent synaptic plasticity. A major plasticity model at glutamatergic synapses is NMDA-receptor (NMDAR)-dependent long-term potentiation (LTP). Ca2+/calmodulin (CaM)-dependent kinase II (CaMKII) is critical for LTP and several forms of learning. It is a major component of post-synaptic densities and dendritic spines. Kinase interactions with key proteins in these specializations are differentially modulated by activity and dynamically regulate holoenzyme activity. During LTP CaMKII is activated, autophosphorylated and persistently translocated to synapses through NMDAR binding. Pharmacological or genetic interference with these processes impair LTP and learning. CaMKII may cause potentiation by synaptic recruitment of AMPA-type receptors (AMPARs) through regulation of receptor binding to scaffolding proteins. Additionally, CaMKII-dependent phosphorylation increases AMPAR conductance. Interestingly, CaMKII is also involved in metaplasticity, as it can regulate the sign of synaptic modification (potentiation or depression). The advent of high-resolution optical techniques has allowed inspection of CaMKII localization and activity in spine microdomains, providing new insights on holoenzyme multifaceted involvement in activity-dependent functional and structural changes. Finally, evidence suggests a role of CaMKII interaction with NMDARs in the maintenance of synaptic strength and spine stability. Thus, CaMKII emerges as a critical and complex controller of synaptic function and information storage, playing both enzymatic and structural roles.


CaMKII Synaptic plasticity NMDA-receptor Dendritic spines CaMKIIN 


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© Springer International Publishing Switzerland 2016

Authors and Affiliations

  1. 1.Department of Biology, Faculty of SciencesUniversity of ChileSantiagoChile
  2. 2.Universidad de los AndesSantiagoChile

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