The regulation of GABAergic nervous system in sleep‑wake states and general anesthesia

Sleep-wake cycles and general anesthesia both involve reversible alterations in consciousness and share important neurobehavioral characteristics; however, their underlying mechanisms remain incompletely understood. As the principal inhibitory neuronal population in the central nervous system, GABAergic neurons play a key regulatory role in regulating transitions between states of consciousness. This review systematically synthesizes evidence from key brain regions-including the brainstem, basal forebrain, thalamus, hypothalamus, amygdala, and ventral striatum-to highlight the functional heterogeneity of GABAergic neuronal subpopulations involved in the regulation of sleep-wake cycles and anesthesia through "direct inhibition" and "disinhibition" mechanisms. We critically evaluate the shared circuit hypothesis of sleep and anesthesia and support a weaker version of this framework. Accordingly, we propose a three-tier classification system in which the neural circuits underlying sleep and anesthesia are categorized as fully shared, partially shared, or completely dissociated. These findings deepen our understanding of the neural mechanisms underlying transitions between states of consciousness and provide new theoretical targets for optimizing anesthetic management and developing therapeutic strategies for disorders of consciousness.