The neuropeptide Galanin is required for homeostatic rebound sleep following increased neuronal activity

Abstract

Sleep pressure homeostatically increases during wake and dissipates during sleep, but the molecular signals and neuronal substrates that measure homeostatic sleep pressure remain poorly understood. A pharmacological assay that generates acute, short-term increases in wakefulness in larval zebrafish, revealed that subsequent rebound sleep is dependent on the intensity of global neuronal activity. Whole brain activity mapping identified preoptic Galanin expressing neurons as selectively active during rebound sleep, and the induction of galanin transcripts was predictive of total rebound sleep time. Galanin is required for sleep homeostasis, as galanin mutants almost completely lack rebound sleep following both pharmacologically induced neuronal activity and physical sleep deprivation. These results suggest that Galanin expressing neurons play a key role in integrating sleep pressure signals derived from global neuronal activity and act as an output arm for the vertebrate sleep homeostat. (word count: 129).