?CaMKII plays a nonenzymatic role in hippocampal synaptic plasticity and learning by targeting ?CaMKII to synapses.

ABSTRACT: The calcium/calmodulin-dependent kinase type II (CaMKII) holoenzyme of the forebrain predominantly consists of heteromeric complexes of the ?CaMKII and ?CaMKII isoforms. Yet, in contrast to ?CaMKII, the role of ?CaMKII in hippocampal synaptic plasticity and learning has not been investigated. Here, we compare two targeted Camk2b mouse mutants to study the role of ?CaMKII in hippocampal function. Using a Camk2b(-/-) mutant, in which ?CaMKII is absent, we show that both hippocampal-dependent learning and Schaffer collateral-CA1 long-term potentiation (LTP) are highly dependent upon the presence of ?CaMKII. We further show that ?CaMKII is required for proper targeting of ?CaMKII to the synapse, indicating that ?CaMKII regulates the distribution of ?CaMKII between the synaptic pool and the adjacent dendritic shaft. In contrast, localization of ?CaMKII, hippocampal synaptic plasticity and learning were unaffected in the Camk2b(A303R) mutant, in which the calcium/calmodulin-dependent activation of ?CaMKII is prevented, while the F-actin binding and bundling property is preserved. This indicates that the calcium/calmodulin-dependent kinase activity of ?CaMKII is fully dispensable for hippocampal learning, LTP, and targeting of ?CaMKII, but implies a critical role for the F-actin binding and bundling properties of ?CaMKII in synaptic function. Together, our data provide compelling support for a model of CaMKII function in which ?CaMKII and ?CaMKII act in concert, but with distinct functions, to regulate hippocampal synaptic plasticity and learning.

SUBMITTER: Borgesius NZ 

PROVIDER: S-EPMC6623068 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature