Dual oscillator structure of human biological clock: Oscillation coupling between the circadian rhythms and sleep-wake cycle and the sites of oscillation

1. 非光性睡眠-觉醒节律伴动非光性授时节律伴动的短暂期人类受试者被强制执行8天的睡眠-觉醒计划，随后是4天的自由运动。在大多数受试者中，血浆褪黑激素节律在强制时间表中表现出相位延迟偏移，表明褪黑激素节律未能进入非光性授时体。另一方面，在所有被检查的受试者中（n=8），睡眠-觉醒节律从强制作息允许睡眠的阶段开始自由波动，这表明睡眠-觉醒节律已经被非光作息所训练。为了了解睡眠-觉醒节律向非光性授时合子转移所需的周期，我们将强制时间表的暴露时间缩短到4天，再缩短到1天。结果，一半的受试者的睡眠-觉醒周期遵循了强制的4天时间表，而另一半则没有。在1天的强制时间安排下，所有受试者的睡眠-觉醒节奏均未能跟上。研究结果表明，夹带有一个数天的短暂期，并且夹带具有振荡性质。2)褪黑激素节律和睡眠-觉醒节律内部同步的重建强制计划终止后，内部非同步的睡眠-觉醒和褪黑激素节律在几天内通过睡眠-觉醒节律的相位提前或延迟转移重新同步。相移的量和方向取决于相移前睡眠开始与血浆褪黑激素节律峰值之间的相关系。即当两种节律的相位差为2 ~ 4小时时，不发生相移。另一方面，相位差为8 ~ 12小时，相移超过6小时。这些发现有力地表明，睡眠-觉醒和血浆褪黑素节律之间存在振荡相互作用。人类SCN的光反应性采用功能磁共振成像技术研究了人类SCN的光反应性。8名受试者暴露在1000 lx的光照下，监测SCN区域神经元活动的变化。只有一种对光刺激有反应，而其他的则没有，这表明人类的视神经网络对光的反应不是很强。少

1. Non-photic entrainment of sleep-wake rhythm1) Transient periods for entrainment of sleep-wake rhythm to the non-photic zeitgeberThe human subjects were foreced to the sleep-wake schedule for 8 days with was followed by a free-run session of 4 days. In most subjects, plasma melatonin rhythms demonstrated phase-delay shifts during the forced schedule, indicating that the melatonin rhythm failed to entrain to the non-photic zeitgeber. On the other hand, in all subjects examined (n=8) the sleep-wake rhythm started to free-rum from the phase where sleep was allowed by the forced schedule, indicating that the sleep-wake rhythm had been etrained by the non-photic schedule.In order to know the cycle needed for the sleep-wake rhythm to entrain to the non-photic zeitgeber, the exposere period to the forced schedule was shortened to 4 days and further 1 day. As a result, the sleep-wake cycle of a half of the subjects entrained to the forced schedule of 4 days, while that of the other half did … More not. To the forced schedule of 1 day, the sleep-wake rhythm in all subjects failed to entrain. The findings indicate that there was a transient period of several days for the entrainment, and that the entrainment was an oscillatory nature.2) Reestablishment of internal synchronization between the melatonin rhythm and sleep-wake rhythmAfter the forced scheduled was termimated, the internally decynchronized sleep-wake and melatonin rhythms were resynchronized in a few days by means of phase-advance or -delay shifts of sleep-wake rhythm. The amount as well as the direction of phase shift depended on the phase-relashionship before the phase-shift between the sleep-onset and the peak of plasma melatonin rhythm. Namely, when the phase difference of the two rhythms was 2 to 4 hours, there was no phase-shift occurred . On the other hand, the phase difference was 8 to 12 hours, the procuded phase-shift exceeded 6 hours. These findings strongly suggested that there was an oscillatory interaction between the sleep-wake and plasma melatonin rhythms.2. Light responsiveness of human SCNLight responsiveness of the human SCN was studied by means of functional MRI. Eight subjects were exposed to light of 1,000 lx and the changes of neuronal activites in the SCN region were monitored. Only one responded to light stimuli but others not, suggesting that that the SCN response to light is not very strong in humans. Less