An emerging link between general anesthesia and sleep
- Department of Neurobiology and Physiology, Center for Sleep and Circadian Biology, Northwestern University, 2205 Tech Drive, 2-160, Evanston, IL 60208
Two of the most enigmatic and challenging problems in neuroscience are the search for the function of sleep and understanding the mechanism by which volatile chemicals can induce general anesthesia. Despite the apparent similarity of sleep and anesthesia to the neophyte, it is widely argued that these brain states are actually apples and oranges, sleep being readily reversible (thankfully), whereas anesthesia is irreversible. In a recent issue of PNAS, Kelz et al. (1) demonstrate that disruption of a specific neural locus involved in normal sleep–wake regulation selectively affects emergence from, but not induction of, general anesthesia. That article demonstrates that waking up from anesthesia uses neural circuits distinct from those necessary to become anesthetized. It also further solidifies the connection between anesthesia and sleep, implicating wake-promoting neural circuitry in selectively contributing to emergence from anesthesia.
Neural loci have been identified that are important for initiation of and emergence from sleep (Fig. 1 and refs. 2 and 3). For example, GABAergic neurons in the hypothalamic ventrolateral preoptic (VLPO) nucleus promote sleep in part by inhibiting arousal-promoting circuits, such as the hypothalamic tuberomammillary nucleus (TMN). Another critical arousal-promoting or -stabilizing locus is the nucleus of orexin-producing neurons in the lateral hypothalamus (4). Progressive loss of orexin-producing neurons results in the human sleep disorder narcolepsy (5, 6). Individuals affected with narcolepsy transition from wakefulness directly to rapid eye movement (REM) sleep, often with accompanying cataplexy (abrupt …
*E-mail: r-allada{at}northwestern.edu
