Hugin⁺neurons link the sleep homeostat to circadian clock neurons

Abstract

Sleep is controlled by homeostatic mechanisms, which drive sleep following periods of wakefulness, and a circadian clock, which regulates sleep timing in a daily cycle. Homeostatic sleep drive sometimes overrides the clock, such that recovery sleep after deprivation occurs outside the normal circadian rest period. However, mechanisms underlying this effect are unknown. We find that sleep-promoting dorsal fan-shaped body (dFB) neurons, effectors of homeostatic sleep in Drosophila, are presynaptic to hugin+ neurons, previously identified as circadian output neurons regulating locomotor activity rhythms. Sleep deprivation decreases hugin+ neuronal activity, which likely suppresses circadian control to promote recovery sleep driven by dFB neurons. Indeed, removal of hugin+ neurons increases sleep-promoting effects of dFB neurons. Trans-synaptic mapping reveals that hugin+ neurons feed back onto s-LNv central clock neurons, which also show Hugin-dependent decreased activity upon sleep loss.These findings identify a circuit-based mechanism through which sleep drive modulates the circadian system to promote recovery sleep following deprivation.

Cholecystokinin/sulfakinin peptide signaling: conserved roles at the intersection between feeding, mating and aggression

“…Nevertheless, the MP1/MP3 neurons appear to be involved in the switching between conflicting behaviors, probably by integrating different types of inputs that relay information about the external and internal environment. Other similar peptidergic brain systems are constituted for example by the four widely arborizing SIFamide-producing neurons that integrate sexual behavior, feeding and sleep by interactions with multiple brain and VNC circuits [ 237 , 267 , 281 , 282 ] and Hugin neurons that integrate homeostatic sleep signals and the circadian clock, and relays locomotor activity output in adults [ 283 , 284 ]. In larvae, Hugin neurons receive gustatory inputs and form a hub between feeding and locomotion [ 251 , 285 ], a function that is not yet explored in adult flies.…”

Getting into rhythm: developmental emergence of circadian clocks and behaviors

“…The Dh44 neurons act through hugin (+) neurons in the subesophageal zone to modulate rest:activity rhythms (76,77). Hugin (+) neurons then appear to feedback onto central clock neurons to regulate sleep (78). SIFa (+) neurons project widely throughout the brain including innervating olfactory neurons in the antennal lobe to regulate appetitive behavior and feeding (79).…”