Synaptic strength of individual spines correlates with bound Ca2+-calmodulin-dependent kinase II.

Both synaptic strength and spine size vary from spine to spine, but are strongly correlated. This gradation is regulated by activity and may underlie information storage. Ca2+-calmodulin-dependent kinase II (CaMKII) is critically involved in the regulation of synaptic strength and spine size. The high amount of the kinase in the postsynaptic density has suggested that the kinase has a structural role at synapses. We demonstrated previously that the bound amount of CaMKIIalpha in spines persistently increases after induction of long-term potentiation, prompting the hypothesis that this amount may correlate with synaptic strength. To test this hypothesis we combined two recently developed methods, two-photon uncaging of glutamate for determining the EPSC of individual spines (uEPSC) and quantitative microscopy for measuring bound CaMKIIalpha in the same spines. We found that under basal conditions the relative bound amount of CaMKIIalpha varied over a 10-fold range and positively correlated with the uEPSC. Both the bound amount of CaMKIIalpha in spines and uEPSC also positively correlated with spine size. Interestingly, the bound CaMKIIalpha fraction (bound/total CaMKIIalpha in spines) remained remarkably constant across all spines. The results are consistent with the hypothesis that bound CaMKII serves as a structural organizer of postsynaptic molecules and thereby may be involved in maintaining spine size and synaptic strength.