Murakoshi, H., Shin, M. E., Parra-Bueno, P., Szatmari, E. M., Shibata, A. C., &
Yasuda, R. (2017). Kinetics of endogenous CaMKII required for synaptic plasticity revealed by
optogenetic kinase inhibitor. Neuron, 94(1), 37-47.
https://www.sciencedirect.com/science/article/pii/S0896627317301447
Invented a genetically encoded, light-inducible inhibitor of CaMKII
Hippocampal slice (MNI-glutamate uncaging and HFS-LTP experiments), mouse
amygdala (inhibitory avoidance memory erasure experiments)
Authors directly test a central hypothesis about LTP and learning –that it is
dependent on an immediate, short-duration rise in Ca2+ concentration in spines (via NMDA
receptors) activating CaMKII’s (auto)phosphorylation ability. They develop, and fully
characterize, a novel, genetically-encoded photoactivatable inhibitor (paAIP2) of CaMKII’s
phosphorylation ability. When paAIP2 is activated by blue light it immediately and reversibly
inhibits CaMKII. Authors demonstrate specificity using western blot experiments. They
demonstrate the time-dependence of CaMKII activation for the structural expression of LTP in
hippocampal slices using MNI-glutamate uncaging experiments. They demonstrate the timedependence of CaMKII activation for the electrophysiological expression of LTP in hippocampal
slice stimulation experiments. Finally, in behaving animal experiments, they demonstrate that
bilateral amygdala photoactivation of paAIP2 during inhibitory avoidance training erases the fear
memory.
“Our study also revealed the temporal requirement of CaMKII activation for HFSinduced LTP to be ~1 min, similar to that for spine structural plasticity (Figure 6). While the
process of glutamate uncaging-evoked spine structural plasticity and HFS-LTP has been
thought to be similar (Matsuzaki et al., 2004), the kinetics of molecular activation during HFSLTP has not been measured. These results suggest that similar signaling cascades are
activated during glutamate uncaging-induced spine structural plasticity and HFS-LTP.”