Phospholipase C-β4 Is Essential for the Progression of the Normal Sleep Sequence and Ultradian Body Temperature Rhythms in Mice
Phospholipase C-β4 Is Essential for the Progression of the Normal Sleep Sequence and Ultradian Body Temperature Rhythms in Mice
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DOI：
10.1371/journal.pone.0007737
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发表时间：
2009-11-09
期刊：
影响因子：
3.7
通讯作者：
Yoshioka, Tohru
中科院分区：
文献类型：
--
作者：
Ikeda, Masayuki;Hirono, Moritoshi;Yoshioka, Tohru
背景资料：睡眠顺序：i）非REM睡眠，ii）REM睡眠，和iii）觉醒，在哺乳动物中是稳定的和广泛保存的，但潜在的机制是未知的。已经表明，在主动觉醒期间，快速眼动睡眠的突然开始会破坏该序列（即，例如，发作性睡病）。磷脂酶C（PLC）介导包括食欲素受体在内的许多代谢型受体的信号传导。在几种PLC亚型中，β 4亚型独特地定位于丘脑的膝状体核，其被假设在睡眠阶段的过渡和维持中具有关键作用。事实上，我们已经报道了PLC-β 4缺陷突变（PLC-β 4-/-）小鼠REM睡眠期间的不规则θ波频率。日常行为表型和代谢型受体参与尚未进行详细分析，在PLC-β 4-/- mice，however.Methodology/Principal Findings：因此，我们分析了24小时睡眠脑电图在PLC-β 4-/- mice。PLC-β 4-/-小鼠在白天和夜间都表现出正常的非REM睡眠。然而，PLC-β 4-/-小鼠在夜间表现出增加的REM睡眠，这是它们的活跃期。此外，他们的睡眠是碎片化的，在白天和晚上都有不寻常的清醒到快速眼动睡眠的过渡。此外，PLC-β 4-/-小鼠在白天降低了超日体温节律和升高的体温，但对环境温度的急性变化（22摄氏度-4摄氏度）有正常的居家反应。在最有可能产生这些行为表型的大脑区域内，我们发现，PLC-β 4-/-小鼠的背外侧膝状体核（LGNd）中，不是食欲素，而是第1组代谢型谷氨酸受体（mGluR）介导的Ca 2+动员显著减少。电压钳记录显示，PLC-β 4-/-小鼠中LGNd中继神经元中第1组mGluR介导的电流（野生型小鼠向内）是向外的。结论/意义：这些证据表明，LGNd中继受损（可能是通过第1组mGluR介导的）可能是PLC-β 4-/-小鼠不规则睡眠序列和超日体温节律的基础。
Background: The sleep sequence: i) non-REM sleep, ii) REM sleep, and iii) wakefulness, is stable and widely preserved in mammals, but the underlying mechanisms are unknown. It has been shown that this sequence is disrupted by sudden REM sleep onset during active wakefulness (i. e., narcolepsy) in orexin-deficient mutant animals. Phospholipase C (PLC) mediates the signaling of numerous metabotropic receptors, including orexin receptors. Among the several PLC subtypes, the beta 4 subtype is uniquely localized in the geniculate nucleus of thalamus which is hypothesized to have a critical role in the transition and maintenance of sleep stages. In fact, we have reported irregular theta wave frequency during REM sleep in PLC-beta 4-deficient mutant (PLC-beta 4-/-) mice. Daily behavioral phenotypes and metabotropic receptors involved have not been analyzed in detail in PLC-beta 4-/- mice, however.Methodology/Principal Findings: Therefore, we analyzed 24-h sleep electroencephalogram in PLC-beta 4-/- mice. PLC-beta 4-/- mice exhibited normal non-REM sleep both during the day and nighttime. PLC-beta 4-/- mice, however, exhibited increased REM sleep during the night, their active period. Also, their sleep was fragmented with unusual wake-to-REM sleep transitions, both during the day and nighttime. In addition, PLC-beta 4-/- mice reduced ultradian body temperature rhythms and elevated body temperatures during the daytime, but had normal homeothermal response to acute shifts in ambient temperatures (22 degrees C-4 degrees C). Within the most likely brain areas to produce these behavioral phenotypes, we found that, not orexin, but group-1 metabotropic glutamate receptor (mGluR)-mediated Ca2+ mobilization was significantly reduced in the dorsal lateral geniculate nucleus (LGNd) of PLC-beta 4-/- mice. Voltage clamp recordings revealed that group-1 mGluR-mediated currents in LGNd relay neurons (inward in wild-type mice) were outward in PLC-beta 4-/- mice.Conclusions/Significance: These lines of evidence indicate that impaired LGNd relay, possibly mediated via group-1 mGluR, may underlie irregular sleep sequences and ultradian body temperature rhythms in PLC-beta 4-/- mice.