CaMKII Autophosphorylation Is Necessary for Optimal Integration of Ca2+ Signals during LTP Induction, but Not Maintenance

Abstract

CaMKII plays a critical role in decoding calcium (Ca²⁺) signals to initiate long-lasting synaptic plasticity. However, the properties of CaMKII that mediate Ca²⁺ signals in spines remain elusive. Here, we measured CaMKII activity in spines using fast-framing two-photon fluorescence lifetime imaging. Following each pulse during repetitive Ca²⁺ elevations, CaMKII activity increased in a stepwise manner. Thr286 phosphorylation slows the decay of CaMKII and thus lowers the frequency required to induce spine plasticity by several fold. In the absence of Thr286 phosphorylation, increasing the stimulation frequency results in high peak mutant CaMKII^T286A activity that is sufficient for inducing plasticity. Our findings demonstrate that Thr286 phosphorylation plays an important role in induction of LTP by integrating Ca²⁺ signals, and it greatly promotes, but is dispensable for, the activation of CaMKII and LTP.

Keywords: CA1 pyramidal neurons; Schaffer collateral; calcium signaling; calmodulin; dendritic spines; hippocampus; signal transduction; synaptic plasticity.