Research ArticleSleep

Mutant neuropeptide S receptor reduces sleep duration with preserved memory consolidation

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Science Translational Medicine  16 Oct 2019:
Vol. 11, Issue 514, eaax2014
DOI: 10.1126/scitranslmed.aax2014

Need for sleep

Sleep is crucial for healthy living and well-being. Sleep need varies greatly among people; however, little is known about the processes regulating sleep duration, continuity, and depth. Here, Xing et al. performed whole exome sequencing in a family of short sleepers and identified a point mutation in the neuropeptide S receptor 1 (NPSR1) gene responsible for the short sleep phenotype. The mutation increased receptor sensitivity to the endogenous ligand. Mice carrying the mutation showed increase mobility time and reduced sleep duration. Moreover, the animals were resistant to cognitive impairment induced by sleep deprivation. The results suggest that NPSR1 might play a major role in sleep-related memory consolidation.


Sleep is a crucial physiological process for our survival and cognitive performance, yet the factors controlling human sleep regulation remain poorly understood. Here, we identified a missense mutation in a G protein–coupled neuropeptide S receptor 1 (NPSR1) that is associated with a natural short sleep phenotype in humans. Mice carrying the homologous mutation exhibited less sleep time despite increased sleep pressure. These animals were also resistant to contextual memory deficits associated with sleep deprivation. In vivo, the mutant receptors showed increased sensitivity to neuropeptide S exogenous activation. These results suggest that the NPS/NPSR1 pathway might play a critical role in regulating human sleep duration and in the link between sleep homeostasis and memory consolidation.

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