Unravelling the cellular mechanisms underlying sleep oscillations

Cortical slow-wave oscillations are a hallmark of non-rapid eye movement sleep in mammals. Their amplitude is considered a classical marker of sleep need, but the mechanisms generating the synchronised UP and DOWN states underpinning slow-wave oscillations remain poorly understood. In the fruit fly, as in mammals, sleep need is represented by the amplitude of slow-wave oscillations, which occur in a small population of sleep-control neurons. These neurons sense sleep need by monitoring the balance between mitochondrial electron supply and ATP demand and translate this signal into cytosolic calcium and transmembrane voltage oscillations. However, how mitochondrial metabolism regulates slow calcium oscillations is unknown. The proposed research will answer this question at single-cell resolution, by combining cutting-edge techniques in physiology, genetics, molecular cell biology, and behaviour in the fruit fly. Unravelling the mechanisms underlying slow oscillations will potentially uncover their link to the cellular restorative functions of sleep and clarify their health implications.