An inhibitory feedback circuit mediating sleep need and sensory gating in Drosophila

Abstract

Many animals integrate sensory information during the day and sleep at night. How sensory processing during wakefulness contributes to making an organism tired at night, however, remains elusive. Here, we investigate the role of excitatory helicon cells in Drosophila (ExR1), a distinct neural population dedicated to processing sensory information. Using combined optogenetics and voltage imaging, we show that helicon cells excite sleep-promoting R3m ring neurons and trigger a subsequent autoinhibition of R3m via voltage- and Ca2+-gated K+ channels such as Slowpoke. Investigating the flies sleep patterns, we found that blocking synaptic output from helicon as well as RNAi-mediated knockdown of Slowpoke in R3m reduces sleep quality and leads to loss of nocturnal sleep, indicating that sleep need is generated via this route. Further, we show that excitation of R3m induces feedback inhibition of helicon cells via ionotropic GABA receptors. Knockdown of the ionotropic GABA receptor subunit Rdl in helicon cells increases sleep latency and causes sleep loss at the beginning of the night. We show that inhibition via Rdl facilitates nocturnal slow-wave activity which forms a sensory filter and prevents sleep disruption through auditory stimuli. We therefore uncover an inhibitory feedback circuit, in which neurons processing sensory information directly activate sleep promoting neurons to generate sleep need. At night, this sleep need is then converted into actual sleep, facilitated by the formation of a neural filter that stabilizes sleep/wake transition.