A specific circuit in the midbrain detects stress and induces restorative sleep

Science. 2022 Jul;377(6601):63-72. doi: 10.1126/science.abn0853. Epub 2022 Jun 30.


In mice, social defeat stress (SDS), an ethological model for psychosocial stress, induces sleep. Such sleep could enable resilience, but how stress promotes sleep is unclear. Activity-dependent tagging revealed a subset of ventral tegmental area γ-aminobutyric acid (GABA)-somatostatin (VTAVgat-Sst) cells that sense stress and drive non-rapid eye movement (NREM) and REM sleep through the lateral hypothalamus and also inhibit corticotropin-releasing factor (CRF) release in the paraventricular hypothalamus. Transient stress enhances the activity of VTAVgat-Sst cells for several hours, allowing them to exert their sleep effects persistently. Lesioning of VTAVgat-Sst cells abolished SDS-induced sleep; without it, anxiety and corticosterone concentrations remained increased after stress. Thus, a specific circuit allows animals to restore mental and body functions by sleeping, potentially providing a refined route for treating anxiety disorders.

MeSH terms

  • Animals
  • Corticotropin-Releasing Hormone / metabolism
  • Hypothalamic Area, Lateral / physiopathology
  • Mice
  • Resilience, Psychological*
  • Sleep*
  • Sleep, REM
  • Social Defeat*
  • Somatostatin / metabolism
  • Stress, Psychological* / physiopathology
  • Ventral Tegmental Area* / physiopathology
  • gamma-Aminobutyric Acid / metabolism


  • Somatostatin
  • gamma-Aminobutyric Acid
  • Corticotropin-Releasing Hormone