A Common Neuroendocrine Substrate for Diverse General Anesthetics and Sleep

Neuron. 2019 Jun 5;102(5):1053-1065.e4. doi: 10.1016/j.neuron.2019.03.033. Epub 2019 Apr 18.

Abstract

How general anesthesia (GA) induces loss of consciousness remains unclear, and whether diverse anesthetic drugs and sleep share a common neural pathway is unknown. Previous studies have revealed that many GA drugs inhibit neural activity through targeting GABA receptors. Here, using Fos staining, ex vivo brain slice recording, and in vivo multi-channel electrophysiology, we discovered a core ensemble of hypothalamic neurons in and near the supraoptic nucleus, consisting primarily of neuroendocrine cells, which are persistently and commonly activated by multiple classes of GA drugs. Remarkably, chemogenetic or brief optogenetic activations of these anesthesia-activated neurons (AANs) strongly promote slow-wave sleep and potentiates GA, whereas conditional ablation or inhibition of AANs led to diminished slow-wave oscillation, significant loss of sleep, and shortened durations of GA. These findings identify a common neural substrate underlying diverse GA drugs and natural sleep and reveal a crucial role of the neuroendocrine system in regulating global brain states. VIDEO ABSTRACT.

Keywords: activity-dependent labeling; general anesthesia; neuroendocrine cells; sleep.

Publication types

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

MeSH terms

  • Anesthesia, General
  • Anesthetics, General / pharmacology*
  • Animals
  • Dexmedetomidine / pharmacology
  • Electroencephalography
  • Electromyography
  • Electrophysiological Phenomena
  • Hypnotics and Sedatives / pharmacology*
  • Hypothalamus / cytology
  • Hypothalamus / drug effects
  • Hypothalamus / metabolism
  • Isoflurane / pharmacology
  • Ketamine / pharmacology
  • Mice
  • Neuroendocrine Cells / drug effects*
  • Neuroendocrine Cells / metabolism
  • Neurons / drug effects
  • Neurons / metabolism
  • Optogenetics
  • Patch-Clamp Techniques
  • Propofol / pharmacology
  • Proto-Oncogene Proteins c-fos / metabolism
  • Sleep / drug effects
  • Sleep / physiology
  • Sleep, Slow-Wave / drug effects*
  • Sleep, Slow-Wave / physiology
  • Supraoptic Nucleus / cytology
  • Supraoptic Nucleus / drug effects*
  • Supraoptic Nucleus / metabolism

Substances

  • Anesthetics, General
  • Fos protein, mouse
  • Hypnotics and Sedatives
  • Proto-Oncogene Proteins c-fos
  • Dexmedetomidine
  • Ketamine
  • Isoflurane
  • Propofol