Neural circuits of non-image-forming vision

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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.