Simultaneous Monitoring of Behavior & Peripheral Clocks in Drosophila Reveals Unstructured Sleep in an Alzheimer’s Model

Sleep and circadian rhythms are ancient, related phenomena controlled by distinct circuitry, whose appropriate regulation is critical to health. The regulatory machinery underlying sleep homeostasis is ill-defined, but biological clock mechanisms are better understood: from clock gene oscillations to rest/activity cycles. Age- and neurodegeneration-related deterioration in sleep/wake timing was first described in humans decades ago, and has recently been recapitulated in model organisms. To delineate causal relationships between aging, sleep, neuronal function and the molecular clockwork, we developed FLYGLOW, a bioluminescence-based system which allows rest/activity, sleep consolidation and molecular rhythms to be quantified simultaneously in many individual flies over days/weeks. FLYGLOW outperforms existing methods, and allows multiparameter correlational analyses within and between flies. We also show unambiguously that peripheral tissue rhythms free-run independently of the central pacemakers driving behavioural cycles. Using an Alzheimers fly model we observe a profound disorganization of sleep/wake cycles, phenocopying the human disease.