Understanding the Neural Mechanisms of General Anesthesia from Interaction with Sleep–Wake State: A Decade of DiscoveryS

Abstract

The development of cutting-edge tech-niques to study specific brain regions and neural circuits that regulate sleep–wake brain states and general anesthesia (GA), has increased our understanding of these states that exhibit similar neurophysiologic traits. This review summarizes current knowledge focusing on cell subtypes and neural circuits that control wakefulness, rapid eye movement (REM) sleep, non-REM sleep, and GA. We also review novel insights into their interactions and raise unre-solved questions and challenges in this field. Com-parisons of the overlapping neural substrates of sleep–wake and GA regulation will help us to understand sleep–wake transitions and how anesthetics cause reversible loss of consciousness. Significance Statement——General anesthesia (GA), sharing numerous neurophysiologic traits with the pro-cess of natural sleep, is administered to millions of surgical patients annually. In the past decade, studies exploring the neural mechanisms underlying sleep–wake and GA have advanced our understanding of their interactions and how anesthetics cause reversible loss of consciousness. Phar-macotherapies targeting the neural substrates associated with sleep–wake and GA regulations have significance for clinical practice in GA and sleep medicine.