<i>Hugin</i> ⁺ neurons provide a link between sleep homeostat and circadian clock neurons

Abstract

Sleep is controlled by homeostatic mechanisms, which drive sleep after wakefulness, and a circadian clock, which confers the 24-h rhythm of sleep. These processes interact with each other to control the timing of sleep in a daily cycle as well as following sleep deprivation. However, the mechanisms by which they interact are poorly understood. We show here that <i>hugin</i>⁺ neurons, previously identified as neurons that function downstream of the clock to regulate rhythms of locomotor activity, are also targets of the sleep homeostat. Sleep deprivation decreases activity of <i>hugin</i>⁺ neurons, likely to suppress circadian-driven activity during recovery sleep, and ablation of <i>hugin</i>⁺ neurons promotes sleep increases generated by activation of the homeostatic sleep locus, the dorsal fan-shaped body (dFB). Also, mutations in peptides produced by the <i>hugin</i>⁺ locus increase recovery sleep following deprivation. Transsynaptic mapping reveals that <i>hugin</i>⁺ neurons feed back onto central clock neurons, which also show decreased activity upon sleep loss, in a Hugin peptide-dependent fashion. We propose that <i>hugin</i>⁺ neurons integrate circadian and sleep signals to modulate circadian circuitry and regulate the timing of sleep.