A half-centre oscillator encodes sleep pressure

Abstract

Oscillatory neural dynamics are an inseparable part of mammalian sleep. Characteristic rhythms are associated with different sleep stages and variable levels of sleep pressure, but it remains unclear whether these oscillations are passive mirrors or active generators of sleep. Here we report that sleep-control neurons innervating the dorsal fan-shaped body of Drosophila (dFBNs) produce slow-wave activity (SWA) in the delta frequency band (0.2-2 Hz) that is causally linked to sleep. The dFBN ensemble contains rhythmic cells whose membrane voltages oscillate in anti-phase between hyperpolarized DOWN and depolarized UP states releasing bursts of action potentials. The oscillations rely on direct interhemispheric competition of two inhibitory half-centers connected by glutamatergic synapses. Interference with glutamate release from dFBNs disrupts SWA and baseline as well as rebound sleep, while the optogenetic replay of SWA (with the help of intersectional, dFBN-restricted drivers) induces sleep. dFBNs generate SWA throughout the sleep-wake cycle-- despite a mutually antagonistic flip-flop arrangement with arousing dopaminergic neurons--but adjust its power to sleep need via an interplay of sleep history-dependent increases in excitability and homeostatic depression of their efferent synapses, as we demonstrate transcriptionally, structurally, functionally, and with a simple computational model. The oscillatory format permits a durable encoding of sleep pressure over long time scales but requires downstream mechanisms that convert the amplitude-modulated periodic signal into binary sleep-wake states.