LAUSR

Significance Although many brain regions have been shown to participate in sleep–wake regulation using model organisms, we sought to identify a region relevant to human sleep duration regulation. We started from a human sleep duration gene (ADRB1) and then used an unbiased approach to identify the peri-tegmental reticular nucleus (pTRNADRB1) as a region participating in sleep–wake regulation. We found that pTRNADRB1 neurons are wake-active and are potent promoters of wakefulness, with their activation promoting wakefulness well after the end of stimulation. Further, combinatorial genetics revealed that excitatory pTRNADRB1 neurons are primarily responsible for this phenotype and that they act in part through projections to the lateral hypothalamus. Thus, the pTRN plays an important role in sleep–wake regulation.