Neural Correlates of Wakefulness, Sleep, and General Anesthesia: An Experimental Study in Rat

Anesthesiology. 2016 Nov;125(5):929-942. doi: 10.1097/ALN.0000000000001342.

Abstract

Background: Significant advances have been made in our understanding of subcortical processes related to anesthetic- and sleep-induced unconsciousness, but the associated changes in cortical connectivity and cortical neurochemistry have yet to be fully clarified.

Methods: Male Sprague-Dawley rats were instrumented for simultaneous measurement of cortical acetylcholine and electroencephalographic indices of corticocortical connectivity-coherence and symbolic transfer entropy-before, during, and after general anesthesia (propofol, n = 11; sevoflurane, n = 13). In another group of rats (n = 7), these electroencephalographic indices were analyzed during wakefulness, slow wave sleep (SWS), and rapid eye movement (REM) sleep.

Results: Compared to wakefulness, anesthetic-induced unconsciousness was characterized by a significant decrease in cortical acetylcholine that recovered to preanesthesia levels during recovery wakefulness. Corticocortical coherence and frontal-parietal symbolic transfer entropy in high γ band (85 to 155 Hz) were decreased during anesthetic-induced unconsciousness and returned to preanesthesia levels during recovery wakefulness. Sleep-wake states showed a state-dependent change in coherence and transfer entropy in high γ bandwidth, which correlated with behavioral arousal: high during wakefulness, low during SWS, and lowest during REM sleep. By contrast, frontal-parietal θ connectivity during sleep-wake states was not correlated with behavioral arousal but showed an association with well-established changes in cortical acetylcholine: high during wakefulness and REM sleep and low during SWS.

Conclusions: Corticocortical coherence and frontal-parietal connectivity in high γ bandwidth correlates with behavioral arousal and is not mediated by cholinergic mechanisms, while θ connectivity correlates with cortical acetylcholine levels.

MeSH terms

  • Acetylcholine / metabolism
  • Anesthesia, General*
  • Anesthetics, Inhalation / pharmacology
  • Anesthetics, Intravenous / pharmacology
  • Animals
  • Cerebellar Cortex / drug effects*
  • Cerebellar Cortex / physiology*
  • Electroencephalography
  • Male
  • Methyl Ethers / pharmacology
  • Models, Animal
  • Propofol / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Sevoflurane
  • Sleep / physiology*
  • Wakefulness / drug effects
  • Wakefulness / physiology*

Substances

  • Anesthetics, Inhalation
  • Anesthetics, Intravenous
  • Methyl Ethers
  • Sevoflurane
  • Acetylcholine
  • Propofol