Activation of Preoptic GABAergic or Glutamatergic Neurons Modulates Sleep-Wake Architecture, but Not Anesthetic State Transitions

Curr Biol. 2020 Mar 9;30(5):779-787.e4. doi: 10.1016/j.cub.2019.12.063. Epub 2020 Feb 20.


The precise mechanism of general anesthesia remains unclear. In the last two decades, there has been considerable focus on the hypothesis that anesthetics co-opt the neural mechanisms regulating sleep. This hypothesis is supported by ample correlative evidence at the level of sleep-promoting nuclei, but causal investigations of potent inhaled anesthetics have not been conducted. Here, we tested the hypothesis that chemogenetic activation of discrete neuronal subpopulations within the median preoptic nucleus (MnPO) and ventrolateral preoptic nucleus (VLPO) of the hypothalamus would modulate sleep/wake states and alter the time to loss and resumption of consciousness associated with isoflurane, a potent halogenated ether in common clinical use. We show that activating MnPO/VLPO GABAergic or glutamatergic neurons does not alter anesthetic induction or recovery time. However, activation of these neuronal subpopulations did alter sleep-wake architecture. Notably, we report the novel finding that stimulation of VLPO glutamatergic neurons causes a strong increase in wakefulness. We conclude that activation of preoptic GABAergic or glutamatergic neurons that increase sleep or wakefulness does not substantively influence anesthetic state transitions. These data indicate that the correlative evidence for a mechanistic overlap of sleep and anesthesia at the level of an individual nucleus might not necessarily have strong causal significance.

Keywords: DREADD; arousal; consciousness; general anesthesia; isoflurane; sleep; wakefulness.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anesthetics, Inhalation / pharmacology*
  • Animals
  • Female
  • GABAergic Neurons / drug effects
  • GABAergic Neurons / physiology
  • Isoflurane / pharmacology*
  • Male
  • Mice
  • Neurons / drug effects
  • Neurons / physiology*
  • Preoptic Area / drug effects
  • Preoptic Area / physiology*
  • Sleep / physiology*
  • Wakefulness / physiology*


  • Anesthetics, Inhalation
  • Isoflurane