Investigating Metabolic Mechanisms Regulating Rhythmic Behavior Development in Drosophila

University Of Arkansas At Fayetteville, Fayetteville AR

Investigators

Linked publications & trials

Abstract

Sleep characteristics change dramatically across development. In early life, sleep duration and depth are elevated, and sleep lacks a strong circadian pattern even though central molecular clocks begin cycling during very early developmental periods. Both sleep and metabolic disturbances are common in neurodevelopmental disorders, emphasizing the need to understand their developmental regulation. Indeed, circadian disruptions are often associated with metabolic disorders like obesity, diabetes, and metabolic syndrome. However, how circadian-sleep and metabolism interact in developing organisms is not well understood. Our goal is to define the cellular and metabolic mechanisms that coordinate maturation of behavioral rhythms. Our research uses the powerful model system Drosophila to gain novel insights into sleep regulation and function across developmental periods. Our studies have identified circuit and molecular mechanisms coordinating emergence of circadian sleep patterns. We developed methods to study sleep patterns in larval stages to accomplish this work and propose to build on those efforts. Previous work demonstrated that Drosophila larvae sleep during the 2nd instar stage (L2), but this sleep lacks a daily rhythm and is not under circadian control. In contrast, a circadian sleep pattern emerges in 3rd instar larvae (L3), with increased sleep duration and depth at night. This change is generated by a new brain connection in L3 that forms between a specific group of clock neurons and arousalpromoting cells. The cues that trigger formation of this clock-arousal circuit are unknown. We aim to examine the hypothesis that metabolic cues play a central role in coordinating the emergence of sleep rhythms. Using diverse experimental approaches, we aim to 1) define the molecular and cellular events that trigger formation of the clock-arousal circuit required for circadian-sleep patterns; 2) investigate cellular mechanisms coupling sleep and feeding behaviors during development; and 3) determine the role of the clock-arousal circuit in regulating sleep timing in adulthood. The proposed research will generate new insights into the establishment of daily sleep and feeding patterns, with implications for dysregulation of these developmental processes in pathological states. The proposed research will utilize the expertise in all three core facilities at the AIMRC to develop automated behavioral feeding analysis approaches (Data Science Core), analyze neural activity in response to metabolic conditions (Imaging Core), and examine changes in cellular energetics across development (Bioenergetics Core). Completion of the proposal will advance my independent career by providing the foundation for future R01 applications and expanding my lab’s research focus into other areas through collaborations.