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Investigating circadian disruption using real-time longitudinal imaging of the entire Drosophila circadian neural network

Abstract

Circadian oscillators are capable of endogenous oscillations in free-running conditions. Many studies show that the coordination of the biological clock with environmental inputs, such as daily solar cycles, is critical for regulating physiological and behavioral activities. Conversely, billions of people worldwide are subjecting themselves to chronic misalignment and disruption of biological clocks with environmental inputs. In this study, we developed an entrainment protocol we call LD Strobe that permits us to obtain real-time, longitudinal bioluminescence imaging of the entire Drosophila circadian neural circuit in adult cultured brains, ex vivo. With the LD Strobe schedule, we can now examine circadian disruptions that could potentially lead to the progression of human-related diseases. In the following proposed projects we aim to (1) capture the Drosophila circuit-wide responses to Weekend Light Shifts, (2) determine Drosophila behavioral outputs generated by circadian-disrupted flies after undergoing a simulated weekend, (3) examine the circuit-wide response of flies in a genetic background with uncharacterized disruptions to circadian-modulated physiology and behavior, and (4) determine the circadian regulation light-evoked attraction and avoidance behaviors in daytime- and nighttime-biting mosquitos. Due to similarities between mammalian and insect circadian molecular and neural circuits, features of the circadian physiological and behavioral outputs from the proposed projects may be broadly observed and applicable to humans.

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