Fig. 9: Schematic depicting how homeostatic sleep drive drives increased seizure risk.

Sleep drive leads to increased activity of sleep-promoting circuits, and we find that this, in part, is driven by decreased expression of 5HT1A in the dorsal fan-shaped body (dFB). Increased activity of sleep-promoting circuits then leads to increased sleep drive, which allows flies to reach the required amount of sleep. This process is known as sleep homeostasis. A “price” of sleep homeostasis is that sustained activation sleep-promoting circuits leads to increased “sleepiness” and increased seizure activity. On the other hand, if the activity of sleep-promoting circuits is decreased (e.g., experimentally with GtACR1 activation or pharmacologically with 5HT1A agonism), seizures are less likely to occur.