The impact of daytime light exposure on diurnal and circadian rhythms in the diurnal rodent Rhabdomys pumillio

在我们的进化史上，地球绕其轴的自转使我们所接触到的光有一个高度可预测的、大振幅的24小时节律。人工照明的出现从两个方面从根本上破坏了这种关系。首先，它让我们在晚上体验到不自然的高强度光线。其次，它允许我们在室内度过大部分醒着的时间，白天暴露在不自然的低光水平下。人们对夜间光线的有害影响给予了极大的关注，来自动物和人类研究的证据表明，夜间光线会扰乱我们生理和行为中确定24小时节律的内源性计时机制（生物钟），抑制睡眠，对整体健康和白天的表现产生连锁反应。相比之下，人们对白天光线强度降低的影响的研究要少得多。这是一个耻辱，因为，虽然我们几乎不可能逆转过去100年的进步，并说服人们在晚上避免使用非自然光源，但通过改变建筑照明设计，甚至只是鼓励人们花更多的时间在户外，增加白天的光线水平是很容易实现的。有来自人类的证据表明，白天增加光照可以提高警觉性和认知能力，从长远来看，它可以改变昼夜节律的相位，增加振幅，降低光敏性。然而，文献很少，缺乏对白天光照水平对时间生理影响的系统研究。在这里，我们着手解决这一缺陷，并询问改变白天光照对24小时行为和生理节律的影响（如果有的话）。然后，我们继续询问白天光强度的增加是否可以改善夜间光的一些破坏性影响。我们将通过研究实验室啮齿动物来解决这些问题。在昼夜节律生物学领域，将实验动物的发现转化为人类有丰富的历史。在实验动物身上工作有一个巨大的优势，它允许研究人员在许多天/几周内仔细控制环境条件，这在实验室的人类研究中很难实现，更不用说在现场条件下了。幸运的是，在实验室中建立的一般原理已被证明对理解现实世界中人类的节律生理有很好的效用。将这种老生常谈的方法应用于本提案中提出的问题的一个重大挑战是，通常使用的实验室啮齿动物（小鼠，大鼠，仓鼠）是夜间活动的，通常不会经历明亮的白天光线。事实上，在实验室里，它们采用行为策略来减少白天暴露在阳光下的时间——筑巢、寻找阴凉处、睡觉时保护眼睛。如果我们要了解昼夜节律组织变化的白天光照水平的影响，以及夜间光线的破坏性影响，因此我们需要一个像人类一样积极寻求白天光照的物种。为了准备这项提议，我们在曼彻斯特建立了一个这种动物的聚居地。横纹肌鼠是一种来自非洲的老鼠，比普通的实验室老鼠稍大。但重要的是，无论是在自然环境中还是在实验室中，它们基本上都是白天活动的。因此，它们也有一个视觉系统，就像我们自己的一样，可以在明亮的光线下看到。在这个提议中，我们将仔细地改变白天光线的强度，并监测对Rhabdomys行为和生理的日常节律的影响。然后我们会问增加白天的光照是否会改善夜间光照的破坏性影响，特别强调人们所经历的那种夜间照明模式。

Throughout our evolutionary history, the rotation of the earth upon its axis imposed a highly predictable and large amplitude twenty four hour rhythm in the amount of light to which we were exposed. The advent of artificial lighting has fundamentally disrupted this relationship in two ways. Firstly, it allows us to experience unnaturally high levels of light at night. Secondly, it allows us to spend most of our waking time indoors, exposed to unnaturally low light levels during the day. Significant attention has been paid to the deleterious effects of light at night, with evidence from both animal and human studies that this disrupts the endogenous timing mechanisms (circadian clocks) that define 24hr rhythms in our physiology and behaviour and inhibits sleep, with knock-on consequences for general health and daytime performance. By contrast, the impact of reduced light intensity during the day has been much less studied. This is a shame because, while it is practically inconceivable that we could reverse the progress of the last >100 years and persuade people to avoid unnatural sources of light at night, increasing levels of daytime light could be readily achieved by changes to architectural lighting design or even just by encouraging people to spend more time outdoors. There is evidence from humans that increasing light during the day improves alertness and cognitive performance, and that in the long term it can change the phase, increase the amplitude, and reduce the photosensitivity of circadian rhythms. However, the literature is sparse and lacks a systematic study of the impact of daytime light levels on temporal physiology. Here we set out to address this deficit and ask what impact, if any, changing daytime light exposure has on 24hr rhythms in behaviour and physiology. We then continue to ask whether increases in daytime light intensity can ameliorate some of the disruptive effects of light at night. We will address these questions by studying laboratory rodents. There is a rich history of translating findings from laboratory animals to humans in the field of circadian biology. Working in laboratory animals has the huge advantage of allowing researchers to carefully control environmental conditions over many days/weeks in a way that is difficult to achieve in human studies in the laboratory, let alone under field conditions. Fortunately, general principles established in the laboratory have proven to have good utility for understanding rhythmic physiology of humans in the real world. A substantial challenge in applying this well-worn approach to the questions posed in this proposal is that commonly employed laboratory rodents (mice, rats, hamsters) are nocturnal and would not normally experience bright daytime light. Indeed, in the lab they employ behavioural strategies to reduce their daytime light exposure - build nests, seek shade, shield their eyes during sleep. If we are to understand the impact of changing daytime light levels on circadian organisation and the disruptive effects of light at night we therefore need a species that, like humans, actively seeks daytime light exposure. We have established a colony of such animals in Manchester in preparation for this proposal. Rhabdomys pumillio is a species of mouse from Africa, slightly larger than ordinary lab mice. Importantly though, in both their natural environment and in the lab they are substantially day active. Accordingly, they also have a visual system that, like our own, is optimised for seeing in bright light. In this proposal we will carefully change the intensity of daytime light and monitor the impact on daily rhythms in behaviour and physiology in Rhabdomys. We will then ask whether increasing daytime light exposure ameliorates the disruptive effects of nighttime light exposure, with especial emphasis on the sort of nocturnal lighting patterns experienced by people.