Sleep drive, not total sleep amount, increases seizure risk.

Sleep loss has been associated with increased seizure risk since antiquity. Using automated video detection of spontaneous seizures in Drosophila epilepsy models, we show that seizures worsen only when sleep restriction raises homeostatic "sleep drive," not simply when total sleep amount falls. This is supported by the paradoxical finding that acute activation of sleep-promoting circuits worsens seizures, because it increases sleep drive without changing sleep amount.

Clock-dependent regulation of a homeostatic sleep center maintains daytime sleep and evening activity.

Homeostatic sleep centers promote sleep in response to prolonged wakefulness, but their contribution to circadian-regulated daily sleep is still unclear. Do neuronal circuits driving rebound sleep after extended wakefulness also drive circadian-gated sleep, or does rebound sleep differ on a neurophysiological level from daily baseline sleep? We observed in Drosophila that 23E10+ neurons, which include a homeostatic sleep center, the dorsal fan-shaped body (dFSB), promote sleep in a time-of-day-dependent manner-the neurons play the strongest role in the maintenance of daytime sleep, and this effect on the siesta maps to cholinergic neurons within the dFSB. We asked whether 23E10+ neurons interact with the circadian clock to regulate daily sleep and find their role in maintaining the daytime siesta is at least partially dependent on the period gene.

Sleepiness, not total sleep amount, increases seizure risk.

Sleep loss has been associated with increased seizure risk since antiquity. Despite this observation standing the test of time, how poor sleep drives susceptibility to seizures remains unclear. To identify underlying mechanisms, we restricted sleep in epilepsy models and developed a method to identify spontaneous seizures using quantitative video tracking.