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Dissecting and modeling photic and melanopsin effects to predict sleep disturbances induced by irregular light exposure in mice [Neuroscience]
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2021-06-22 , DOI: 10.1073/pnas.2017364118
Jeffrey Hubbard 1, 2 , Mio Kobayashi Frisk 1, 2 , Elisabeth Ruppert 1, 2 , Jessica W Tsai 3 , Fanny Fuchs 1, 2 , Ludivine Robin-Choteau 1, 4 , Jana Husse 5 , Laurent Calvel 1, 2 , Gregor Eichele 5 , Paul Franken 6 , Patrice Bourgin 2, 7
Affiliation  

Artificial lighting, day-length changes, shift work, and transmeridian travel all lead to sleep–wake disturbances. The nychthemeral sleep–wake cycle (SWc) is known to be controlled by output from the central circadian clock in the suprachiasmatic nuclei (SCN), which is entrained to the light–dark cycle. Additionally, via intrinsically photosensitive retinal ganglion cells containing the photopigment melanopsin (Opn4), short-term light–dark alternations exert direct and acute influences on sleep and waking. However, the extent to which longer exposures typically experienced across the 24-h day exert such an effect has never been clarified or quantified, as disentangling sustained direct light effects (SDLE) from circadian effects is difficult. Recording sleep in mice lacking a circadian pacemaker, either through transgenesis (Syt10cre/creBmal1fl/-) or SCN lesioning and/or melanopsin-based phototransduction (Opn4−/−), we uncovered, contrary to prevailing assumptions, that the contribution of SDLE is as important as circadian-driven input in determining SWc amplitude. Specifically, SDLE were primarily mediated (>80%) through melanopsin, of which half were then relayed through the SCN, revealing an ancillary purpose for this structure, independent of its clock function in organizing SWc. Based on these findings, we designed a model to estimate the effect of atypical light–dark cycles on SWc. This model predicted SWc amplitude in mice exposed to simulated transequatorial or transmeridian paradigms. Taken together, we demonstrate this SDLE is a crucial mechanism influencing behavior on par with the circadian system. In a broader context, these findings mandate considering SDLE, in addition to circadian drive, for coping with health consequences of atypical light exposure in our society.



中文翻译:


解剖和模拟光和黑视蛋白效应,以预测小鼠不规则光照引起的睡眠障碍 [神经科学]



人工照明、日长变化、轮班工作和跨子午线旅行都会导致睡眠-觉醒障碍。众所周知,夜间睡眠-觉醒周期(SWc)是由视交叉上核(SCN)中的中央生物钟的输出控制的,该时钟伴随着明暗周期。此外,通过含有光色素黑视蛋白(Opn4)的本质光敏视网膜神经节细胞,短期明暗交替对睡眠和清醒产生直接而剧烈的影响。然而,通常在 24 小时内经历的较长时间暴露所产生的这种影响的程度从未得到澄清或量化,因为将持续直接光效应 (SDLE) 与昼夜节律效应区分开来是很困难的。通过转基因( Syt10 cre/cre Bmal1 fl/- )或SCN损伤和/或基于黑视蛋白的光转导( Opn4 −/− )记录缺乏昼夜节律起搏器的小鼠的睡眠,我们发现,与普遍的假设相反,贡献在确定 SWc 幅度时,SDLE 的值与昼夜节律驱动的输入一样重要。具体来说,SDLE 主要通过黑视蛋白介导(>80%),其中一半随后通过 SCN 传递,揭示了该结构的辅助目的,独立于其组织 SWc 的时钟功能。基于这些发现,我们设计了一个模型来估计非典型光暗循环对 SWc 的影响。该模型预测了暴露于模拟跨赤道或跨子午线范式的小鼠的 SWc 振幅。综上所述,我们证明了 SDLE 是与昼夜节律系统同等影响行为的关键机制。 在更广泛的背景下,这些发现要求除了昼夜节律驱动之外,还应考虑使用 SDLE 来应对我们社会中非典型光暴露的健康后果。

更新日期:2021-06-22
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