Kinetics of Endogenous CaMKII Required for Synaptic Plasticity Revealed by Optogenetic Kinase Inhibitor.
Kinetics of Endogenous CaMKII Required for Synaptic Plasticity Revealed by Optogenetic Kinase Inhibitor.
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DOI：
10.1016/j.neuron.2017.02.036
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发表时间：
2017-04-05
期刊：
影响因子：
16.2
通讯作者：
Yasuda R
中科院分区：
文献类型：
--
作者：
Murakoshi H;Shin ME;Parra-Bueno P;Szatmari EM;Shibata ACE;Yasuda R
阐明突触和行为可塑性所需的信号活动的时间窗口对于理解这些现象背后的分子机制至关重要。在这里，我们开发了光激活自体抑制肽2(PaAIP2)，它是一种遗传编码的、光诱导的CaMKII活性抑制物。在LTP的诱导过程中，神经元中paAIP2的光激活1-2min和树突的结构LTP(SLTP)抑制了啮齿动物海马片的这些形式的可塑性。然而，诱导后约1min的光激活对它们没有影响，提示CaMKII最初1min的激活足以诱导LTP和sLTP。此外，在抑制回避任务中，小鼠杏仁核神经元中表达的paAIP2的光激活表明，记忆形成需要在训练期间而不是训练后的CaMKII活性。因此，我们证明了paAIP2对于阐明突触可塑性和学习所需的CaMKII激活的时间窗是有用的。Murakoshi和Shin等人。开发了一种光诱导的CaMKII抑制剂，并证明了短暂的蓝光照射到表达该抑制剂的神经元会阻止突触的可塑性和学习。
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 and Shin et al. developed a light-inducible inhibitor of CaMKII and demonstrated that a brief illumination of blue light to neurons expressing this inhibitor blocks synaptic plasticity and learning.