Altered stimulus representation in rat auditory cortex is not causal for loss of consciousness under general anaesthesia

Br J Anaesth. 2018 Sep;121(3):605-615. doi: 10.1016/j.bja.2018.05.054. Epub 2018 Jun 28.

Abstract

Background: Current concepts suggest that impaired representation of information in cortical networks contributes to loss of consciousness under anaesthesia. We tested this idea in rat auditory cortex using information theory analysis of multiunit responses recorded under three anaesthetic agents with different molecular targets: isoflurane, propofol, and dexmedetomidine. We reasoned that if changes in the representation of sensory stimuli are causal for loss of consciousness, they should occur regardless of the specific anaesthetic agent.

Methods: Spiking responses were recorded with chronically implanted microwire arrays in response to acoustic stimuli incorporating varied temporal and spectral dynamics. Experiments consisted of four drug conditions: awake (pre-drug), sedation (i.e. intact righting reflex), loss of consciousness (a dose just sufficient to cause loss of righting reflex), and recovery. Measures of firing rate, spike timing, and mutual information were analysed as a function of drug condition.

Results: All three drugs decreased spontaneous and evoked spiking activity and modulated spike timing. However, changes in mutual information were inconsistent with altered stimulus representation being causal for loss of consciousness. First, direction of change in mutual information was agent-specific, increasing under dexmedetomidine and decreasing under isoflurane and propofol. Second, mutual information did not decrease at the transition between sedation and LOC for any agent. Changes in mutual information under anaesthesia correlated strongly with changes in precision and reliability of spike timing, consistent with the importance of temporal stimulus features in driving auditory cortical activity.

Conclusions: The primary sensory cortex is not the locus for changes in representation of information causal for loss of consciousness under anaesthesia.

Keywords: consciousness; dexmedetomidine; isoflurane; neocortex; propofol.

MeSH terms

  • Acoustic Stimulation / methods
  • Anesthesia, General / methods*
  • Anesthetics, General / pharmacology*
  • Anesthetics, Inhalation / pharmacology
  • Anesthetics, Intravenous / pharmacology
  • Animals
  • Auditory Cortex / drug effects*
  • Auditory Cortex / physiology
  • Consciousness / drug effects*
  • Consciousness / physiology
  • Dexmedetomidine / pharmacology
  • Electroencephalography / drug effects
  • Female
  • Hypnotics and Sedatives / pharmacology
  • Isoflurane / pharmacology
  • Propofol / pharmacology
  • Rats, Inbred ACI
  • Reaction Time / drug effects
  • Reflex, Righting / drug effects
  • Reflex, Righting / physiology

Substances

  • Anesthetics, General
  • Anesthetics, Inhalation
  • Anesthetics, Intravenous
  • Hypnotics and Sedatives
  • Dexmedetomidine
  • Isoflurane
  • Propofol