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

The development of cutting-edge tech-niques to study specific brain regions and neural cir-cuits that regulate sleep-wake brain states and general anesthesia (GA), has increased our under-standing of these states that exhibit similar neuro-physiologic traits. This review summarizes current knowledge focusing on cell subtypes and neural cir-cuits 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 re-versible 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.