Bittman Eric L
Department of Biology and Program in Neuroscience and Behavior, University of Massachusetts, Amherst, MA, USA.
J Biol Rhythms. 2014 Apr;29(2):97-109. doi: 10.1177/0748730413520399.
The duper mutation in Syrian hamsters shortens the free-running period (τDD) of locomotor activity by approximately 1 h when expressed on the wild-type background and by 2 h on the tau mutant background ("super duper"). In either case, duper markedly amplifies the phase response curve (PRC) of the light pulse. This work examined whether the duper mutation alters parametric as well as nonparametric properties, intensity thresholds, and noncircadian responses to light. Furthermore, it assessed the effects of duper on the range of entrainment and circadian aftereffects. In the first study, duper mutant and wild-type (wt) hamsters showed a similar intensity threshold for light-induced phase shifts. In the second, wt, tau mutant, and super duper hamsters were exposed to LD cycles whose period (T) progressively shortened. Regardless of whether the light phase was held at 50% of T or fixed at 3 h, super duper mutants entrained to a wider range of T cycles and showed aftereffects upon release into DD. In the third study, τLL was measured in mutant and wt hamsters that were maintained for 30-day intervals in constant light of progressively greater intensities. With increasing light intensity, the circadian period shortened in duper mutants. Circadian rhythms of super duper hamsters were disrupted at light intensities considerably below those that induced arrhythmicity in wt, tau heterozygote, or duper homozygote hamsters. In the fourth study, hamsters that were wt or homozygous for duper received two 15-min light pulses: the first at CT14 to CT16 or CT17 to CT19 and the second 2 h later. As expected, wt and duper mutants showed weak and strong resetting, respectively. Light pulses in early subjective night had an additive effect in mutant but not in wt hamsters, indicating that larger phase shifts of the pacemaker take longer to complete. Finally, super duper hamsters showed slightly but not significantly more negative masking than did wt or duper mutant hamsters. These results indicate that the duper mutation affects the properties of the central circadian pacemaker. The mutant allele affects not only the PRC but also parametric responses to light.
叙利亚仓鼠中的“超级复制”突变在野生型背景下表达时,会使运动活动的自由运转周期(τDD)缩短约1小时,在tau突变背景下(“超级超级复制”)则缩短2小时。在这两种情况下,“超级复制”都会显著放大光脉冲的相位响应曲线(PRC)。本研究探讨了“超级复制”突变是否会改变参数以及非参数特性、强度阈值和对光的非昼夜反应。此外,还评估了“超级复制”对同步范围和昼夜后效应的影响。在第一项研究中,“超级复制”突变仓鼠和野生型(wt)仓鼠对光诱导的相位移动表现出相似的强度阈值。在第二项研究中,wt、tau突变仓鼠和“超级超级复制”仓鼠暴露于周期(T)逐渐缩短的LD循环中。无论光期是保持在T的50%还是固定为3小时,“超级超级复制”突变体都能同步到更广泛的T周期范围内,并且在释放到DD后表现出后效应。在第三项研究中,在逐渐增加强度的持续光照下,每隔30天对突变仓鼠和wt仓鼠的τLL进行测量。随着光照强度的增加,“超级复制”突变体的昼夜周期缩短。“超级超级复制”仓鼠的昼夜节律在光照强度远低于诱导wt、tau杂合子或“超级复制”纯合子仓鼠出现节律紊乱的强度时就被破坏了。在第四项研究中,wt或“超级复制”纯合的仓鼠接受两个15分钟的光脉冲:第一个在CT14至CT16或CT17至CT19,第二个在2小时后。正如预期的那样,wt和“超级复制”突变体分别表现出微弱和强烈的重置。早期主观夜间的光脉冲在突变仓鼠中具有累加效应,而在wt仓鼠中则没有,这表明起搏器更大的相位移动需要更长时间才能完成。最后,“超级超级复制”仓鼠表现出比wt或“超级复制”突变仓鼠略多但不显著的负性掩蔽。这些结果表明,“超级复制”突变会影响中枢昼夜起搏器的特性。突变等位基因不仅影响PRC,还影响对光的参数反应。