Calcium/calmodulin-dependent protein kinase II contributes to activity-dependent filopodia growth and spine formation.

Remodeling of synaptic networks through an activity-dependent formation or elimination of synaptic connections is believed to contribute to information processing and long-term memory. Recent work showed that enhanced synaptic activation, including induction of long-term potentiation and sensory stimulation, promote a rapid growth of dendritic filopodia and the formation of new spines or new types of synapses. Here, we investigated whether calcium/calmodulin-dependent protein kinase II (CaMKII), an enzyme implicated in the control of synaptic efficacy, also participated in these mechanisms. We show that the intracellular application of autophosphorylated CaMKII reproduced these morphological changes and triggered filopodia growth and spine formation. In addition, we find that activation of endogenous kinase through the inhibition of phosphatases or the application of calmodulin in the cell produced similar effects. Conversely, blockade of CaMKII activity prevented the synaptic enhancement, the growth of filopodia and formation of new spines triggered by LTP induction, and a short anoxia/hypoglycemia. Together, these results support the interpretation that CaMKII contributes to the control of activity-dependent structural plasticity.