A half-centre oscillator encodes sleep need in the Drosophila brain

Homeostatic regulation of sleep and wakefulness is essential for survival, but the underlying mechanisms are poorly understood. In Drosophila, a central role in sleep homeostasis is attributed to neurons projecting to the dorsal fan-shaped body (dFB), which store sleep need via their intrinsic excitability. Here, we test if and how dFB neurons incorporate this intrinsic account of sleep drive into their network activity. In vivo dFB neuron ensemble activity is rhythmic, with a peak at 0.2-1 Hz (measured via calcium imaging). The amplitude of these slow oscillations increases with sleep drive, and their optogenetic replay using a dFB neuron-restricted driver line promotes sleep. While this corroborates analogies to mammalian slow-wave sleep, our experiments also reveal an important distinction: dFB neurons receive and can modulate arousal signals (via mutually-inhibitory connections with arousal-mediating dopamine neurons), but their oscillations persist during arousal. Moreover, slow oscillations in dFB neurons originate from a confined central pattern generator, which is anticorrelated between hemispheres and relies on mutually-inhibitory connections. Accordingly, blocking dFB neuronal output disrupts oscillations and sleep. Lastly, these output synapses undergo homeostatic plasticity upon sleep deprivation, which might be used to maintain robust dFB neuron network activity. Our experiments provide direct functional evidence for the involvement of dFB neural activity in the control of sleep in Drosophila, and reveal that these neurons harbour a half-centre oscillator that generates a neural code for sleep need.