Photoactivatable CaMKII induces synaptic plasticity in single synapses

Optogenetic approaches for studying neuronal functions have proven their utility in the neurosciences. However, optogenetic tools capable of inducing synaptic plasticity at the level of single synapses have been lacking. Here, we engineered a photoactivatable (pa)CaMKII by fusing a light-sensitive domain, LOV2, to CaMKII alpha. Blue light or two-photon excitation reversibly activated paCaMKII. Activation in single spines was sufficient to induce structural long-term potentiation (sLTP) in vitro and in vivo. paCaMKII activation was also sufficient for the recruitment of AMPA receptors and functional LTP in single spines. By combining paCaMKII with protein activity imaging by 2-photon FLIM-FRET, we demonstrate that paCaMKII activation in clustered spines induces robust sLTP via a mechanism that involves the actin-regulatory small GTPase, Cdc42. This optogenetic tool for dissecting the function of CaMKII activation (i.e., the sufficiency of CaMKII rather than necessity) and for manipulating synaptic plasticity will find many applications in neuroscience and other fields. Optogenetic control of molecules is important in cell biology and neuroscience. Here, the authors describe an optogenetic tool to control the Ca2+/calmodulin-dependent protein kinase II and use it to control plasticity at the single synapse level.

Automated summary

The study introduces a photoactivatable CaMKII tool to control synaptic plasticity at the single synapse level by optogenetic means, shedding light on the sufficiency of CaMKII activation for inducing structural long-term potentiation, and can have important applications in neuroscience research.