Kinetics of Endogenous CaMKII Required for Synaptic Plasticity Revealed by Optogenetic Kinase Inhibitor.
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.
Supportive Center for Brain Research, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan; Department of Physiological Sciences, Graduate University for Advanced Studies, Okazaki, Aichi 444-8585, Japan; Japan Science and Technology Agency (JST), Kawaguchi, Saitama 332-0012, Japan; Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: murakosh@nips.ac.jp.
Hideji
H
Murakoshi
Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA.
Myung Eun
ME
Shin
Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA.
Paula
P
Parra-Bueno
Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA.
Erzsebet M
EM
Szatmari
Supportive Center for Brain Research, National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan.
Akihiro C E
ACE
Shibata
Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA; Max Planck Florida Institute for Neuroscience, Jupiter, FL 33458, USA. Electronic address: ryohei.yasuda@mpfi.org.
Ryohei
R
Yasuda
D000818:Animals; D000831:Animals, Newborn; D001362:Avoidance Learning / Q000502:physiology*; D056547:CA1 Region, Hippocampal / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D049229:Dendritic Spines / Q000378:metabolism* / Q000502:physiology; D004591:Electrophoresis, Polyacrylamide Gel; D057809:HEK293 Cells; D006367:HeLa Cells; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007700:Kinetics; D017774:Long-Term Potentiation / Q000502:physiology; D051379:Mice; D008856:Microscopy, Fluorescence; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000502:physiology; D062308:Optogenetics; D017966:Pyramidal Cells / Q000378:metabolism* / Q000502:physiology; D016601:RNA-Binding Proteins; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins / Q000235:genetics
C569621:Paip2 protein, mouse; D016601:RNA-Binding Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D025521:Tumor Suppressor Proteins; C000621448:paAIP2 protein; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2
FLIM; FRET; LTP; amygdala; dendritic spines; hippocampus; mice; signaling; structural plasticity