CaMKIIα 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 CaMKIIα integrates Ca2+ 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 Ca²⁺ signals over ~10 s under this condition, the integration of Ca2+ signal by CaMKIIα during spine structural plasticity is largely due to Ca²⁺/CaM-independent, autonomous activity. Based on these results, we propose a simple kinetic model of CaMKIIα activation in dendritic spines.
Mechanisms of Ca²⁺/calmodulin-dependent kinase II activation in single dendritic spines
Representative fluorescence lifetime images of the novel sensor CaMKIIα-CaM that can report the CaMKII activity that is dependent on its association with CaM, in response to glutamate uncaging to simulate plasticity in single synapses. Warmer colors indicate lower fluorescence lifetime, corresponding to a higher activity.
Max Planck Florida Institute for Neuroscience
