Loss of <i>Arc</i> attenuates the behavioral and molecular responses for sleep homeostasis in mice
Ayako Suzuki, Masashi Yanagisawa, Robert Greene
Abstract
Significance Arc is a neural immediate early gene involved in synaptic downscaling and is robustly induced by prolonged wakefulness in rodent brains. However, it remains unclear if and how Arc is involved in sleep regulation. Here we find that Arc is important for inducing multiple homeostatic responses induced by sleep deprivation at behavioral and molecular levels: (1) rebound of sleep time; (2) expression of a subset of sleep deprivation-induced genes; and (3) synaptic glutamate receptor expression. In sleep-deprived wild-type brains, Arc protein levels are significantly increased in the nucleus, cytoplasm, and synapse, suggesting multiple roles for Arc depending on its subcellular location. These findings provide the functional evidence for the role of Arc in homeostatic sleep regulation.