Adaptation to Jet Lag in Animal Models

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DESCRIPTION (provided by applicant): Circadian rhythms are entrained daily to the environmental light-dark (LD) cycle of 24h by a central pacemaker. The entrained rhythms are disrupted following a shift of the LD cycle (when traveling across time zones), in shiftwork, and following sleep deprivations. It is widely recognized that large inter-individual variations exist in how humans cope with disruptions of circadian rhythms. While a large number of factors contribute to how fast circadian rhythms reentrain following such disruptions, it is not known what parameters of the circadian timing system determine the rate of adaptation. Adaptation of disrupted rhythms to a new time zone was investigated in rodents using pineal melatonin as a clock marker. We have found that (1) reentrainment to a delayed LD cycle is a slow process; (2) a large inter-individual variation exists in timings of melatonin onset under entrained conditions in outbred animals; (3) the timing of melatonin onset is a function of photoperiod (length of the light period); and (4) a large inter-individual variation exists in rate of reentrainment following a delay shift of the LD cycle in outbred rats. Remarkably, we have discovered a tight association between the timing of melatonin onset and the rate of reentrainment. In this revised proposal, we plan to further investigate the relationship between timings of melatonin secretion and rate of reentrainment in rodents. Aim 1 will test the hypothesis that the earlier the melatonin onset, the faster animals reentrain following a delay shift of the LD cycle, regardless the magnitude of the shift. In Aim 2, we will determine the relationship between onset timings of melatonin secretion and intrinsic period of rodents and test the hypothesis that shorter the circadian period, faster the individual reentrains following a delay shift of the LD cycle, regardless the magnitude of the shift. Aim 3 will examine the relationship between rate of reentrainment and timing of melatonin onset in both short and long photoperiod to test the hypothesis that the shorter the night period, the faster the individual reentrains following a delay shift of the LD cycle, regardless the magnitude of the shift. The goal is to establish an unambiguous relationship between the rate of reentrainment and timing of melatonin onset. The proposed studies will impact our basic understanding of circadian rhythm reentrainment, and will benefit our understanding of how humans cope with circadian disruptions such as jet lag, shift work, and sleep deprivations.