Calcium/calmodulin kinase II in the pedunculopontine tegmental nucleus modulates the initiation and maintenance of wakefulness.
Calcium/calmodulin kinase II in the pedunculopontine tegmental nucleus modulates the initiation and maintenance of wakefulness.
复制标题
DOI：
10.1523/jneurosci.3981-11.2011
复制
发表时间：
2011-11-23
期刊：
影响因子：
--
通讯作者：
Patterson EH
中科院分区：
文献类型：
--
作者：
Datta S;O'Malley MW;Patterson EH
脚桥被盖核（PPT）在觉醒（W）和快速眼动（REM）睡眠的调节中起着关键作用，但我们对这种调节机制的理解仍然不完全。本研究旨在确定PPT细胞内钙/钙调蛋白激酶（CaMKII）信号转导在W和睡眠调节中的作用。为了实现这一目标，三种不同浓度（0.5，1.0，和2.0 nmol）的CaMKII激活抑制剂，KN-93，双侧（100 nl/网站）的PPT自由活动的大鼠，和W，慢波睡眠（SWS），REM睡眠，磷酸化CaMKII（pCaMKII）的PPT表达水平的影响进行了定量。这些影响，这是浓度依赖性和影响的觉醒-睡眠变量为3小时，导致W减少，由于W事件的数量和持续时间的减少;增加SWS和REM睡眠，由于事件持续时间的增加;和PPT中的pCaMKII表达水平降低。回归分析显示，PPT水平与总的睡眠时间百分比呈正相关（R2 = 0.864; n = 28; p < 0.001），与总的睡眠时间百分比呈负相关（R2 = 0.863; p < 0.001）。这些数据提供了第一个直接证据，即PPT中细胞内CaMKII信号的激活促进W并抑制睡眠。这些发现与设计一种通过提高警觉性来治疗过度嗜睡的药物有关。
The pedunculopontine tegmentum nucleus (PPT) is critically involved in the regulation of wakefulness (W) and rapid eye movement (REM) sleep, but our understanding of the mechanisms of this regulation remains incomplete. The present study was designed to determine the role of PPT intracellular calcium/calmodulin kinase (CaMKII) signaling in the regulation of W and sleep. To achieve this aim, three different concentrations (0.5, 1.0, and 2.0 nmol) of the CaMKII activation inhibitor, KN-93, were microinjected bilaterally (100 nl/site) into the PPT of freely moving rats, and the effects on W, slow-wave sleep (SWS), REM sleep, and levels of phosphorylated CaMKII (pCaMKII) expression in the PPT were quantified. These effects, which were concentration-dependent and affected wake–sleep variables for 3 h, resulted in decreased W, due to reductions in the number and duration of W episodes; increased SWS and REM sleep, due to increases in episode duration; and decreased levels of pCaMKII expression in the PPT. Regression analyses revealed that PPT levels of pCaMKII were positively related with the total percentage of time spentin W (R2 = 0.864; n = 28 rats; p < 0.001) and negatively related with the total percentage of time spentin sleep (R2 = 0.863; p < 0.001). These data provide the first direct evidence that activation of intracellular CaMKII signaling in the PPT promotes W and suppresses sleep. These findings are relevant for designing a drug that could treat excessive sleepiness by promoting alertness.