Sleep induction by repetitive mechanosensory stimulation. - Project Summary Sleep is essential for a healthy mind and body and is conserved from invertebrates to humans. Sleep serves multiple functions, including memory consolidation, clearance of harmful metabolites, and prevention of oxidative stress and premature death. Accumulating evidence suggests a bidirectional relationship between sleep and neurodegenerative diseases such as Alzheimer’s disease (AD). AD patients often suffer from sleep disruptions, while disrupted sleep accelerates AD pathologies. Importantly, improved sleep can ameliorate memory deficits in a Drosophila model of AD, suggesting that sleep-related interventions could be an effective strategy for treating AD patients. Sleep is regulated by multiple processes, including sensory processes. Anecdotal observations suggest that babies sleep better when gently rocked or bounced, and several experimental studies have confirmed that rocking promotes sleep in humans and mice. However, the underlying mechanisms for this intriguing phenomenon are not well understood. Fly sleep is similar to human sleep, and our recent finding that gentle vibration promotes sleep in flies provides an opportunity for uncovering the mechanisms of sleep induction by mechanical stimulation. We found that flies sleep longer during vibration and sleep shorter afterward, suggesting vibration-induced sleep (VIS) leads to the accumulation of sleep credit. Preliminary data suggest VIS can also rescue memory deficits due to sleep loss and enhance resistance to oxidative stress. Flies with reduced GABA signaling do not sleep more during vibration, and preliminary data suggest that signaling through a neuropeptide called Diuretic Hormone 44 is also involved in VIS. Building on these results, the proposed studies will investigate whether VIS confers cognitive and health benefits of normal sleep in Drosophila models of AD and discover molecular and neural mechanisms underlying VIS. Our work will provide a novel platform to study the mechanisms of sleep regulation by repetitive mechanosensory stimulation and may suggest a non-invasive sleep-related intervention for AD patients.