JournalNeural Excitability, Synapses, and Glia

Kinetics of Endogenous CaMKII Required for Synaptic Plasticity Revealed by Optogenetic Kinase Inhibitor

This is a schematic of paAIP2. LOV2-Jα domain derived from phototropin1 was fused to autocamtide-2 related inhibitory peptide 2 (AIP2). The blue light absorption causes a reversible conformational change of LOV2 domain, leading to dissociation of the Jα helix-AIP2. The structurally released AIP2 binds to the kinase domain of CaMKII and inhibits its kinase activity.

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  • PaAIP2 is a genetically encoded, light-inducible inhibitor of CaMKII
  • PaAIP2 inhibits CaMKII with high specificity and with second-to-minute temporal resolution
  • PaAIP2 measures the temporal window of CaMKII required for synaptic plasticity
  • PaAIP2 measures the kinetics of CaMKII activity during learning and memory

Summary

Elucidating temporal windows of signaling activity required for synaptic and behavioral plasticity is crucial for understanding molecular mechanisms underlying these phenomena. Here, we developed photoactivatable autocamtide inhibitory peptide 2 (paAIP2), a genetically encoded, light-inducible inhibitor of CaMKII activity. The photoactivation of paAIP2 in neurons for 1–2 min during the induction of LTP and structural LTP (sLTP) of dendritic spines inhibited these forms of plasticity in hippocampal slices of rodents. However, photoactivation ∼1 min after the induction did not affect them, suggesting that the initial 1 min of CaMKII activation is sufficient for inducing LTP and sLTP. Furthermore, the photoactivation of paAIP2 expressed in amygdalar neurons of mice during an inhibitory avoidance task revealed that CaMKII activity during, but not after, training is required for the memory formation. Thus, we demonstrated that paAIP2 is useful to elucidate the temporal window of CaMKII activation required for synaptic plasticity and learning.

Murakoshi, H., Shin, M.E., Parra-Bueno, P., Szatmari, E.M., Shibata, A.C.E., and Yasuda, R. Kinetics of Endogenous CaMKII Required for Synaptic Plasticity Revealed by Optogenetic Kinase Inhibitor. Neuron.
DOI: http://dx.doi.org/10.1016/j.neuron.2017.02.036

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