Independent circadian oscillations of Period1 in specific brain areas in vivo and in vitro

Independent circadian oscillations of Period1 in specific brain areas in vivo and in vitro
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DOI:
10.1523/jneurosci.2225-05.2005
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发表时间:
2005-09-21
影响因子:
5.3
通讯作者:
Herzog, ED
Herzog, ED
中科院分区:
医学1区
文献类型:
--
作者:
Abraham, U;Prior, JL;Herzog, ED

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哺乳动物的行为和生理昼夜节律由下丘脑视交叉上核(SCN)的主起搏器控制。最近,在其他脑区的外植体中也发现了激素分泌、时钟基因表达和电活动的昼夜振荡。这表明,一些SCN以外的大脑区域包含一个功能性的、SCN独立的生物钟,但在体内仍然缺乏内在起搏的证据。我们发展了一种新的方法,从完整的和SCN损伤(SCNX)周期1::荧光素酶的大鼠的主要嗅球(OB)的体内生物发光成像2d的可变黑暗。OBS在原位表达昼夜节律,从白天到夜晚可靠地增加了一倍,与体外节律的相位和幅度相似。在没有SCN的情况下,体内循环至少持续1个月。为了间接评估其他脑区的活体节律性,我们测量了它们的体外节律与手术时间的相位相关性。手术可靠地重置了取自SCNX大鼠的松果体和终板血管器官(VOLT)的时相,但对OB时相几乎没有影响。我们推测,SCN和OB含有自我维持的昼夜节律振荡器,而松果体和Volt是需要从SCN输入的弱振荡器,以显示协调的昼夜节律。我们的结论是,哺乳动物的大脑由一组不同的SCN依赖和SCN非依赖的昼夜节律振荡器组成。
Behavioral and physiological circadian rhythms in mammals are controlled by a master pacemaker in the hypothalamic suprachiasmaticnuclei(SCN). Recently, circadian oscillations of hormone secretion, clock gene expression, and electrical activity have been demonstrated in explants of other brain regions. This suggests that some extra-SCN brain regions contain a functional, SCN-independent circadian clock, but in vivo evidence for intrinsic pacemaking is still lacking. We developed a novel method to image bioluminescence in vivo from the main olfactory bulbs (OB) of intact and SCN-lesioned (SCNX) Period1:: luciferase rats for 2d inconstant darkness. The OBs expressed circadian rhythms in situ with a reliable twofold increase from day to night, similar to the phase and amplitude of ex vivo rhythms. In vivo cycling persisted for at least 1 month in the absence of the SCN. To assess indirectly in vivo rhythmicity of other brain areas, we measured the phase-dependence of their in vitro rhythms on the time of surgery. Surgery reliably reset the phase of the pineal gland and vascular organ of the lamina terminalis (VOLT) harvested from SCNX rats but had little effect on the phase of the OB. We deduce that the SCN and OB contain self-sustained circadian oscillators, whereas the pineal gland and VOLT are weak oscillators that require input from the SCN to show coordinated circadian rhythms. We conclude that the mammalian brain comprises a diverse set of SCN-dependent and SCN-independent circadian oscillators.