A novel neural pathway linking visual input and sleep status

At least 30% of adults suffer sleep-related problems. Sleep disruption can contribute to a variety of medically-relevant problems, including cardiovascular and neuropsychiatric dysfunction. Environmental light and visual stimuli affect both sleep quantity and quality in various animals including insects, birds, mammals and humans. Although the biological basis of such a widely observed phenomenon remains unclear, the latest research and technical advances in the fruit fly, Drosophila, have made it feasible to identify the underlying neural mechanisms. Recently, we have demonstrated that a gene called Neurocalcin is required to modulate neuronal activities in the fly visual system for robust night-time sleep. We plan to use cutting-edge genetic, behavioural and imaging techniques to investigate how Neurocalcin interacts with other genes to control neuronal properties and discover the neural pathways that the visual system communicates with the central brain to regulate sleep. This project promises to address an important knowledge gap in sleep research. Moreover the human homologues of Neurocalcin are also expressed in the eyes and the brain. Therefore, the results from this project may provide insight into how natural and artificial light-related visual stimuli contribute to, and disturb, human sleep.

Sleep disorders are prevalent in the modern 24/7 society and contribute to several medical problems, including cardiovascular, psychiatric and neurodegenerative diseases. A major challenge in sleep research is to determine the relative contributions of genetic versus environmental factors that underlie sleep disorders. It is well established that levels of daylight and daytime visual stimuli have profound effects on the sleep homeostat. The fruit fly, Drosophila, has a proven record as a powerful research tool to provide mechanistic insights into sleep disorders. Importantly, recent research advances in identifying both sleep centres and their potential neural connections to visual system have set the stage for investigating the functional neural pathway by which visual inputs modulate sleep. Against this background, our preliminary data show that a calcium binding protein, Neurocalcin (Nca) is required to modulate neuronal activities in the fly visual system for robust night-time sleep. This finding leads to an exciting hypothesis that Nca-expressed visual domains drives night-specific sleep. Using the latest behavioural, genetic and imaging tools, we will test this hypothesis, and define the role of Nca-linked molecular networks in regulating sleep, and the neural pathways connecting visual system and sleep centres. The project investigate an emergent research direction and the yield results promise to address a knowledge gap in sleep research. Moreover since Nca protein shares >85% amino-acid identity with its mammalian homologues, this proposal will provide a roadmap for investigating conserved molecular mechanisms underlying visually-driven sleep and pave the way for follow-up investigations to validate the role of Nca in mammalian sleep. This may foster further research that significantly advances the understanding in how natural and artificial light-related visual stimuli contributes to human sleep disorder and related medical conditions.