Neural circuits of non-image-forming vision

人类有一种强烈的倾向，低估了他们的行为在多大程度上是由潜意识过程决定的。因此，例如，我们认为眼睛是视觉感知的起源，但忽略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。它通过测量周围环境的光照水平来完成后一项任务，在我们的进化史上（直到最近的电灯出现），光照水平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，这些区域专门调节所谓的非图像形成（NIF）视觉过程，包括设置“生物钟”、调节睡眠、激素系统和瞳孔大小。特别是，通过对生物钟的作用，光强度间接调节从运动能力到认知表现的几乎所有身体过程。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为重要，因为它们正常功能的破坏（如可能发生在轮班工人、商务旅行者或各种神经系统疾病的后果）与严重的健康后果有关。其中包括睡眠和代谢紊乱、癌症、抑郁症以及与工作有关的事故风险增加。目前，我们知道一个相互连接的大脑区域网络控制着这些对光的潜意识反应，但我们对这些不同的大脑区域如何相互作用产生这些反应知之甚少。具体来说，我们知道这些区域中的每一个都包含不同类型的细胞，这些细胞使用不同的化学信使进行交流，但我们不知道这些细胞类型中哪些是相互连接的。这一点尤其重要，因为对大脑网络的现有研究告诉我们，它们许多最重要的特性是通过细胞之间的相互作用产生的，而不是由组成它们的单个细胞固有的。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目前神经科学面临的主要挑战。关于大脑如何利用环境光线水平的信息来调节生理，我建议解决我们知识中的这些实质性空白。使用尖端的实验和理论方法，本研究将确定NIF视觉系统中的哪些细胞与哪些细胞通信，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，以响应外部照明环境。这种对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，具有实质性的治疗和实际意义。这些应用包括确定我们可以设计新药的目标或特定的时间窗口，在这些时间窗口内药物或光应用将最有效地纠正系统功能障碍，例如发生在正常衰老，精神健康障碍，轮班工作或跨越时区时。此外，这项工作可能会为光本身作为治疗工具开辟新的途径；潜在地允许对各种身体系统的选择性操作，而没有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.