Circadian Integration of Photic and Non-photic Stimuli

描述(由申请人提供)：有效地重置内部生物钟对于适应时差和治疗昼夜睡眠障碍是必要的。虽然人们普遍认为光和非光刺激可以使内部昼夜节律计时系统相移，但人们对光和非光时间线索如何整合以产生人体生物钟的光相移知之甚少。主要在非人类身上进行的研究结果表明，昼夜节律计时系统整合了光和非光信息。我们假设人类的昼夜计时系统也整合了光信息和非光信息。如果光和非光时间信号的组合增强了人类的相移，这样的发现将对治疗与昼夜节律相关的睡眠障碍和快速适应时差具有重要意义。我们建议评估由强光照射和非光学提示相结合引起的人体生物钟的相位延迟和相位推进。目前的拨款建议是为了提高我们对各种刺激，如光或内源性因素导致睡眠和昼夜节律的机制的理解。这项研究的新颖之处在于，它提议进行一系列研究，旨在系统地检查光和非光信息被人类昼夜节律时钟整合的能力，从而导致人类昼夜节律计时系统的相移增强。我们预计，拟议的研究结果可能对开发新的时差和睡眠障碍治疗方法具有重要意义，这些疾病会导致患者比预期更晚或更早上床睡觉。拟议的治疗方法可能还会对改善太空飞行等环境中的睡眠状况产生影响。

DESCRIPTION (provided by applicant): Effective resetting of the internal circadian clock is necessary for circadian adaptation to jet lag and for the treatment of circadian sleep disorders. While it is generally recognized that photic and non-photic stimuli can phase shift the internal circadian timekeeping system, little is known about how photic and non-photic time cues are integrated to produce photic phase shifts of the human circadian clock. Results from studies predominantly conducted in non-humans indicate that photic and non-photic information is integrated by the circadian time keeping system. We hypothesize that photic and non-photic information is also integrated by the circadian time keeping system in humans. If the combination of photic and non-photic time cues enhances phase shifts in humans, such a finding would have important implications for the treatment of circadian-related sleep disorders and for rapid adaptation to jet lag. We propose to evaluate phase delays and phase advances of the human circadian clock induced by the combination of bright light exposure with non-photic cues. The current grant proposal is to improve our understanding of the mechanisms through which various stimuli such as light or endogenous factors entrain sleep and circadian rhythms. The research is novel in that it proposes to conduct a series of studies designed to systematically examine the ability of photic and non-photic information to be integrated by the human circadian clock and thus result in enhanced phase shifts of the human circadian timing system. We anticipate that the results of the proposed study may have significant implications for developing new treatments for jet lag and for sleep disorders that cause patients to go to bed much later or earlier than desired. The proposed treatments may also have implications for improving sleep in environments such as space flight.