Mechanisms of Ca(2+)/calmodulin-dependent kinase II activation in single dendritic spines

CaMKIIα plays an essential role in decoding Ca(2+) signaling in spines by acting as a leaky Ca(2+) integrator with the time constant of several seconds. However, the mechanism by which CaMKIIα integrates Ca(2+) signals remains elusive. Here, we imaged CaMKIIα-CaM association in single dendritic spines using a new FRET sensor and two-photon fluorescence lifetime imaging. In response to a glutamate uncaging pulse, CaMKIIα-CaM association increases in ~0.1 s and decays over ~3 s. During repetitive glutamate uncaging, which induces spine structural plasticity, CaMKIIα-CaM association did not show further increase but sustained at a constant level. Since CaMKIIα activity integrates Ca(2+) signals over ~10 s under this condition, the integration of Ca(2+) signal by CaMKIIα during spine structural plasticity is largely due to Ca(2+)/CaM-independent, autonomous activity. Based on these results, we propose a simple kinetic model of CaMKIIα activation in dendritic spines.