Manoogian Emily N C, Leise Tanya L, Bittman Eric L
Department of Biology and Program in Neuroscience and Behavior, University of Massachusetts, Amherst, Massachusetts
Department of Mathematics & Statistics, Amherst College, Amherst, Massachusetts.
J Biol Rhythms. 2015 Apr;30(2):129-43. doi: 10.1177/0748730414568297. Epub 2015 Jan 29.
The duper mutation in Syrian hamsters shortens the free-running period of locomotor activity (τDD) to about 23 h and results in a type 0 phase-response curve (PRC) to 15-min light pulses. To determine whether exaggerated phase shifts are specific to photic cues and/or restricted to subjective night, we subjected hamsters to novel wheel confinements and dark pulses during subjective day. Small phase shifts elicited by the nonphotic cue were comparable in mutant and wild-type (WT) hamsters, but dark pulses triggered larger shifts in dupers. To assess further the effects of the duper mutation on light-dark transitions, we transferred hamsters between constant light (LL) and constant dark (DD) or between DD and LL at various circadian phases. Duper hamsters displayed significantly larger phase shifts than WT hamsters when transferred from LL to DD during subjective day and from DD to LL during subjective night. The variability of phase shifts in response to all light/dark transitions was significantly greater in duper hamsters at all time points. In addition, most duper hamsters, but none of the WTs, displayed transient ultradian wheel-running patterns for 5 to 12 days when transferred from light to dark at CT 18. The χ(2) periodogram and autocorrelation analyses indicate that these ultradian patterns differ from the disruption of rhythmicity by SCN lesions or exposure to constant bright light. We conclude that the duper mutation specifically amplifies phase shifts to photic cues and may destabilize coupling of circadian organization upon photic challenge due to weakened coupling among components of the circadian pacemaker. Mathematical modeling of the circadian pacemaker supports this hypothesis.
叙利亚仓鼠中的“骗子”突变将运动活动的自由运转周期(τDD)缩短至约23小时,并导致对15分钟光脉冲的0型相位响应曲线(PRC)。为了确定夸张的相位偏移是否特定于光信号线索和/或仅限于主观夜间,我们在主观白天对仓鼠进行了新的转轮限制和暗脉冲实验。非光信号线索引起的小相位偏移在突变体和野生型(WT)仓鼠中相当,但暗脉冲在“骗子”仓鼠中引发了更大的偏移。为了进一步评估“骗子”突变对明暗转换的影响,我们在不同的昼夜节律阶段将仓鼠在持续光照(LL)和持续黑暗(DD)之间或在DD和LL之间转移。当在主观白天从LL转移到DD以及在主观夜间从DD转移到LL时,“骗子”仓鼠表现出比WT仓鼠明显更大的相位偏移。在所有时间点,“骗子”仓鼠对所有明暗转换的相位偏移变异性都明显更大。此外,当在CT 18从光转移到暗时,大多数“骗子”仓鼠,但没有一只WT仓鼠,表现出5至12天的短暂超日转轮模式。χ(2)周期图和自相关分析表明,这些超日模式不同于视交叉上核(SCN)损伤或暴露于持续强光对节律性的破坏。我们得出结论,“骗子”突变特异性地放大了对光信号线索的相位偏移,并且由于昼夜节律起搏器各组成部分之间的耦合减弱,在光刺激下可能会破坏昼夜节律组织的耦合。昼夜节律起搏器的数学模型支持这一假设。