A Circuit Mechanism Underlying Suppression of Circadian Signals by Homeostatic Sleep Drive

Sleep is controlled by homeostatic mechanisms, which drive sleep after wakefulness, and a circadian clock, which confers the 24-hour 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 hugin+ 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 hugin+ neurons, likely to suppress circadian-driven activity during recovery sleep, and manipulations of hugin+ neurons affect sleep increases generated by activation of the homeostatic sleep locus, the dorsal fanshaped body (dFB). Also, mutations in peptides produced by the hugin+ locus increase recovery sleep following deprivation. Trans-synaptic mapping reveals that hugin+ neurons feed-back onto central clock neurons, which also show decreased activity upon sleep loss, in a Hugin-peptide dependent fashion. We propose that hugin+ neurons integrate circadian and sleep signals to modulate circadian circuitry and regulate the timing of sleep.