Mechanisms of Ca2+/calmodulin-dependent kinase II activation in single dendritic spines

CaMKII alpha plays an essential role in decoding Ca2+ signaling in spines by acting as a leaky Ca2+ integrator with the time constant of several seconds. However, the mechanism by which CaMKII alpha integrates Ca2+ signals remains elusive. Here, we imaged CaMKII alpha-CaM association in single dendritic spines using a new FRET sensor and two-photon fluorescence lifetime imaging. In response to a glutamate uncaging pulse, CaMKII alpha-CaM association increases in similar to 0.1 s and decays over similar to 3 s. During repetitive glutamate uncaging, which induces spine structural plasticity, CaMKII alpha-CaM association did not show further increase but sustained at a constant level. Since CaMKII alpha activity integrates Ca2+ signals over similar to 10 s under this condition, the integration of Ca2+ signal by CaMKII alpha during spine structural plasticity is largely due to Ca2+/CaM-independent, autonomous activity. Based on these results, we propose a simple kinetic model of CaMKII alpha activation in dendritic spines.