Neural circuits of non-image-forming vision

人类有一种强烈的倾向，会低估他们的行为在多大程度上受到潜意识过程的影响。因此，例如，我们认为眼睛是视觉感知的起源，但忽视了它在根据一天中的时间调整我们的生理和行为方面同样重要的作用。它通过测量环境照度来完成后一项任务，在我们的进化史上(实际上直到最近电照明的出现)，环境照度提供了一天中准确的时间指示。这些关于环境光线水平的信息被传递给大脑的一组区域，这些区域专门调节这些所谓的非成像(NIF)视觉过程，包括设置“生物钟”、调节睡眠、荷尔蒙系统和瞳孔大小。特别是，通过对生物钟的作用，光强度间接地调节了几乎所有的身体过程，从运动能力到认知表现。除了它们在调节“健康”生理方面的关键作用外，了解这些潜意识的光反应尤其重要，因为它们的正常功能中断(如轮班工作人员、商务旅行者或各种神经疾病的结果)已与严重的健康后果有关。这些疾病包括睡眠和代谢障碍、癌症、抑郁症和与工作相关的事故风险增加。目前，我们知道一个相互连接的大脑区域网络控制着这些潜意识对光的反应，但我们对这些不同的大脑区域如何相互作用来产生这些反应知之甚少。具体地说，我们知道这些区域中的每一个都包含各种类型的细胞，这些细胞使用不同的化学信使进行通信，但我们不知道这些细胞类型中的哪些相互连接。这一点尤其重要，因为现有的对大脑网络的研究告诉我们，它们的许多最重要的特性是通过细胞之间的相互作用产生的，而不是组成它们的单个细胞所固有的。事实上，了解这些细胞相互作用如何使大脑发挥其许多功能，是神经科学目前面临的主要挑战。我建议解决我们关于大脑如何利用环境光水平的信息来调节生理的知识中的这些重大空白。使用尖端的实验和理论方法，这项研究将确定NIF视觉系统中的哪些细胞与其他哪些细胞通信，它们如何相互影响，以及它们如何与其他大脑系统通信，以调节生理和行为对外部照明环境的反应。对NIF视觉系统的详细了解将使我们能够设计出更有效的策略来调节它，具有重大的治疗和实际意义。这些应用包括识别目标，我们可以针对这些目标设计新药或特定的时间窗口，在这些时间窗口中，药物或灯光应用将在纠正系统功能障碍方面最有效，例如在正常衰老、精神健康障碍、轮班工作或跨越时区时发生的功能障碍。此外，这项工作可能会为光本身作为一种治疗工具开辟新的途径；有可能允许选择性地操纵各种身体系统，而不会出现与药物治疗相关的副作用。

Humans have a strong tendency to underestimate the degree to which their behaviour is defined by sub-conscious processes. Thus, for example, we think of the eye as the origin of visual perception, but ignore its equally important role in adjusting our physiology and behaviour according to time of day. It achieves this latter task by measuring the level of ambient illumination, which throughout our evolutionary history (indeed until the recent advent of electric lighting) has provided accurate indication of time of day. This information about ambient light levels is communicated a set of brain regions that specifically regulate these so-called non-image forming (NIF) visual processes, including setting the 'body-clock', regulation of sleep, hormonal systems and pupil size. In particular, through actions on the body clock, light intensity indirectly regulates almost all body processes from athletic ability to cognitive performance. Aside from their key role in regulating 'healthy' physiology, understanding these subconscious light responses is particularly important since disruption of their normal functioning (as can occur in shift workers, business travellers or as a consequence of various neurological disorders) has been linked to serious health consequences. These include sleep and metabolic disorders, cancer, depression and increased risk of work-related accidents. At present we know that a network of interconnected brain regions control these subconscious responses to light, yet we have very little idea how these different brain regions interact to produce these responses. Specifically, we know that each of these regions contains various types of cells which use different chemical messengers to communicate, but we do not know which of these cell types connect to one another. This is particularly important because existing studies of brain networks tell us that many of their most important properties arise through the interactions between cells rather than being inherent to the individual cells that make them up. Indeed, understanding how these cellular interactions enable the brain to perform its many functions is currently the major challenge facing neuroscience. I propose to address these substantial gaps in our knowledge as to how the brain uses information about ambient light levels to regulate physiology. Using cutting edge experimental and theoretical approaches this research will determine which cells in the NIF visual system communicate with which other cells, how they influence each other and how they communicate to other brain systems to regulate physiology and behaviour in response to the external lighting environment. This detailed understanding of the NIF visual system will put us in a position to devise more effective strategies to modulate it, with substantial therapeutic and practical implications. These applications include the identification of targets against which we can design new drugs or particular time-windows at which drugs or light application would be most effective at correcting dysfunction of the system such as occur in normal ageing, mental health disorders, shift work or when crossing time zones. Moreover, this work may potentially open up new avenues for the use of light as a therapeutic tool in its own right; potentially allowing for the selective manipulation of various body systems without the side effects that associated with pharmacological treatments.