Ono Daisuke, Honma Sato, Honma Ken-Ichi
Photonic Bioimaging Section, Research Center for Cooperative Projects, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
Department of Chronomedicine, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo, 060-8638, Japan.
Eur J Neurosci. 2015 Dec;42(12):3128-37. doi: 10.1111/ejn.13111.
The temporal order of physiology and behaviour in mammals is regulated by the coordination of the master circadian clock in the suprachiasmatic nucleus (SCN) and peripheral clocks in various tissues outside the SCN. Because the circadian oscillator(s) in the olfactory bulb (OB) is regarded as SCN independent, we examined the relationship between the SCN master clock and the circadian clock in the OB. We also examined the role of vasoactive intestinal peptide receptor 2 in the circadian organization of the OB. We continuously monitored the circadian rhythms of a clock gene product PER2 in the SCN and OB of freely moving mice by means of a bioluminescence reporter and an optical fibre implanted in the brain. Robust circadian rhythms were detected in the OB and SCN for up to 19 days. Bilateral SCN lesions abolished the circadian behaviour rhythms and disorganized the PER2 rhythms in the OB. The PER2 rhythms in the OB showed more than one oscillatory component of a similar circadian period, suggesting internal desynchronization of constituent oscillators. By contrast, significant circadian PER2 rhythms were detected in the vasoactive intestinal peptide receptor 2-deficient mice, despite the substantial deterioration or abolition of circadian behavioural rhythms. These findings indicate that the circadian clock in the OB of freely moving mice depends on the SCN master clock but not on the circadian behavioural rhythms. The circadian PER2::LUC rhythm in the cultured OB was as robust as that in the cultured SCN but reset by slice preparation, suggesting that culturing of the slice reinforces the circadian rhythm.
哺乳动物生理和行为的时间顺序由视交叉上核(SCN)中的主生物钟与SCN外各种组织中的外周生物钟的协调来调节。由于嗅球(OB)中的生物钟振荡器被认为独立于SCN,我们研究了SCN主生物钟与OB中生物钟之间的关系。我们还研究了血管活性肠肽受体2在OB昼夜节律组织中的作用。我们通过植入大脑的生物发光报告基因和光纤,连续监测自由活动小鼠SCN和OB中时钟基因产物PER2的昼夜节律。在OB和SCN中检测到了长达19天的强劲昼夜节律。双侧SCN损伤消除了昼夜行为节律,并使OB中的PER2节律紊乱。OB中的PER2节律显示出多个具有相似昼夜周期的振荡成分,表明组成振荡器的内部不同步。相比之下,尽管昼夜行为节律严重恶化或消失,但在血管活性肠肽受体2缺陷小鼠中检测到了显著的昼夜PER2节律。这些发现表明,自由活动小鼠OB中的生物钟依赖于SCN主生物钟,而不依赖于昼夜行为节律。培养的OB中的昼夜PER2::LUC节律与培养的SCN中的节律一样强劲,但通过切片制备重置,这表明切片培养增强了昼夜节律。