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两个耦合的生物钟振荡器参与了小鼠非光性重新同步到移位光周期的加速过程。

Two Coupled Circadian Oscillators Are Involved in Nonphotic Acceleration of Reentrainment to Shifted Light Cycles in Mice.

机构信息

Department of Physiology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.

Laboratory of Life and Health Sciences, Hokkaido University Graduate School of Education, Sapporo, Japan.

出版信息

J Biol Rhythms. 2018 Dec;33(6):614-625. doi: 10.1177/0748730418796300. Epub 2018 Sep 4.

DOI:10.1177/0748730418796300
PMID:30178701
Abstract

The onset and offset of an activity band in the circadian behavioral rhythm are known to differentially reentrain to shifted light-dark cycles (LD). Differential reentrainment could be explained by different light responsivities of circadian oscillators underlying these phase-markers. In contrast, reentrainment is accelerated by exposure to nonphotic time cues such as timed wheel-running. However, the relationship between the 2 oscillators and nonphotic acceleration of reentrainment is largely unknown. We examined phase-shifts of the mouse behavioral rhythm in response to an 8-h phase-advanced shift of LD and effects of behavioral interventions: maintained in a home cage (HC), exposed to a running wheel (RW) in HC (HC+RW), transferred to a new cage (NC), and exposed to RW in NC (NC+RW). Each intervention was given for 3h from the beginning of the shifted dark period and repeated for 4 days. Following the last dark period, the mice were released into constant darkness (DD). As a result, activity onset and offset were differentially phase-shifted. The activity onset on the first day of DD (DD1) was phase-advanced from the baseline slightly in HC and HC+RW, substantially in NC+RW, but not significantly in NC. The amount of phase-shift was significantly larger in the NC+RW than in the other groups. In contrast, the activity offset was significantly advanced in all groups by 6 to 8 h. The differential phase-shifts resulted in shortening of the activity band (α compression). The α compression was gradually relieved upon exposure to DD (α decompression), and the activity band finally became stable. Interestingly, the magnitude of phase-shifts of activity offset, but not of activity onset, in the following DD was negatively correlated with the extent of α compression in DD1. These findings indicate that the 2 circadian oscillators underlying activity onset and offset are involved in asymmetric phase-shifts and nonphotic acceleration of reentrainment.

摘要

活动带在昼夜节律行为中的开始和结束时间已知会以不同的方式重新同步到移位的明暗周期(LD)。这种不同的重新同步可以用作为这些相位标记基础的生物钟振荡器的不同光反应性来解释。相比之下,暴露于非光照时间线索(如定时轮跑)会加速重新同步。然而,这两个振荡器之间的关系以及重新同步的非光照加速在很大程度上是未知的。我们检查了小鼠行为节律对 LD 相位提前 8 小时的相位移动的反应,以及行为干预的效果:保持在饲养笼中(HC)、在饲养笼中暴露于轮跑(HC+RW)、转移到新笼中(NC)和在 NC 中暴露于轮跑(NC+RW)。每个干预措施从移位的暗期开始后进行 3 小时,并重复 4 天。在最后一个暗期之后,将小鼠释放到持续黑暗中(DD)。结果,活动开始和结束时间以不同的方式发生相位移动。在 DD1 中,活动开始时间相对于基线在 HC 和 HC+RW 中略有提前,在 NC+RW 中明显提前,但在 NC 中没有显著提前。NC+RW 组的相位移动量明显大于其他组。相比之下,所有组的活动结束时间都提前了 6 到 8 小时。不同的相位移动导致活动带变窄(α 压缩)。在暴露于 DD 后,α 压缩逐渐缓解(α 解压),活动带最终稳定下来。有趣的是,在接下来的 DD 中,活动结束时间的相位移动幅度,而不是活动开始时间的相位移动幅度,与 DD1 中的α 压缩幅度呈负相关。这些发现表明,活动开始和结束时间背后的两个生物钟振荡器参与了不对称的相位移动和重新同步的非光照加速。

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