Emerging data suggest that, in addition to sleep amount, sleep quality is important for human health and performance. However, the molecular and neural pathways underlying sleep quality remain unclear. Drosophila is now well-established as a model organism for studying sleep, and my preliminary behavioral and electrophysiological data in Drosophila define a new molecular pathway linking the circadian clock to temporal-specific neural coding to regulate sleep quality. These findings suggest that sleep quality is determined by clock-driven temporal coding in an arousal circuit. Thus, in the proposed work, I will study the relationship between sleep and temporal coding in specific neural circuits. Specifically, I will (1) characterize the molecular mechanisms mediating sleep quality, (2) examine circuit mechanisms underlying temporal coding of sleep quality, and (3) investigate how ionic flux regulates temporal coding of sleep quality. My long-term career goal is to become an independent scientist in academia, and my long-term research goal is to understand how neural coding emerges from specific spike sequences to generate behavioral states such as sleep. To achieve these goals, I will undertake extensive training in molecular biology and biochemistry, in vivo functional imaging, and computational modeling. This new training will complement by previous background in patch-clamp electrophysiology, signal processing skills, Drosophila genetics, and behavioral analyses. The Johns Hopkins University and my mentors and consultants will provide a stellar environment for my scientific growth and guidance in career development. The proposed fellowship will allow me to build my own area of research in neuroscience, and be a competitive investigator with broad expertise from biology to engineering and from molecular and cellular neuroscience to computational neuroscience.
Sleep quality is important for human health, but the mechanisms regulating this process remain unclear. In this proposed work, I will study how the circadian clock uses specific neural coding mechanisms to regulate sleep quality, which should lead to a deeper understanding of the molecular and circuit basis for sleep.
|Tabuchi, Masashi; Monaco, Joseph D; Duan, Grace et al. (2018) Clock-Generated Temporal Codes Determine Synaptic Plasticity to Control Sleep. Cell 175:1213-1227.e18|