A Rare Mutation of β 1-Adrenergic Receptor Affects Sleep/Wake Behaviors

Neuron. 2019 Sep 25;103(6):1044-1055.e7. doi: 10.1016/j.neuron.2019.07.026. Epub 2019 Aug 28.

Abstract

Sleep is crucial for our survival, and many diseases are linked to long-term poor sleep quality. Before we can use sleep to enhance our health and performance and alleviate diseases associated with poor sleep, a greater understanding of sleep regulation is necessary. We have identified a mutation in the β1-adrenergic receptor gene in humans who require fewer hours of sleep than most. In vitro, this mutation leads to decreased protein stability and dampened signaling in response to agonist treatment. In vivo, the mice carrying the same mutation demonstrated short sleep behavior. We found that this receptor is highly expressed in the dorsal pons and that these ADRB1+ neurons are active during rapid eye movement (REM) sleep and wakefulness. Activating these neurons can lead to wakefulness, and the activity of these neurons is affected by the mutation. These results highlight the important role of β1-adrenergic receptors in sleep/wake regulation.

Keywords: ADRB1; dorsal pons; familial natural short sleep; sleep duration.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Gene Knock-In Techniques
  • Humans
  • Mice
  • Mutation
  • Neurons / metabolism
  • Pedigree
  • Pontine Tegmentum / cytology
  • Pontine Tegmentum / metabolism
  • Receptors, Adrenergic, beta-1 / genetics*
  • Sleep / genetics*
  • Sleep Wake Disorders / genetics
  • Sleep, REM / genetics
  • Wakefulness / genetics*

Substances

  • ADRB1 protein, human
  • Adrb1 protein, mouse
  • Receptors, Adrenergic, beta-1