Consciousness, Anesthesia, and Acetylcholine

Cortical acetylcholine concentration tracks with the capacity for conscious experience: high during wakefulness, low during slow-wave sleep, and high again during REM sleep when dreaming occurs. General anesthetics produce parallel changes—GABAergic drugs like propofol and sevoflurane lower acetylcholine and reduce the probability of experience, while non-GABAergic drugs like ketamine and nitrous oxide raise acetylcholine and increase the likelihood of dreams or hallucinations. Interventions that raise brain acetylcholine reverse anesthetic traits or reduce potency in humans and rodents, whereas lesions of cholinergic neurons in the basal forebrain reduce anesthetic requirements for isoflurane and propofol.

Study at a glance

Abstract

Although the precise neural correlates of consciousness have not yet been identified, there is one neurochemical marker that appears to track with our capacity to experience something: acetylcholine concentration in the cerebral cortex. Cortical acetylcholine concentration is high during wakefulness, decreases during slow-wave sleep, and increases again during rapid eye movement sleep, when we can have the conscious experience of dreaming.1 Based on the neuropharmacology of the particular anesthetic drug we might choose, the state of general anesthesia shows parallel changes. For example, effects of the GABAergic anesthetics propofol and sevoflurane are similar to slow-wave sleep and include low acetylcholine concentration, slower electroencephalographic frequency, and a low probability of experience2,3 By contrast, effects of the non-GABAergic anesthetics ketamine and nitrous oxide are similar to rapid eye movement sleep and include high acetylcholine concentration, faster electroencephalographic frequency, and a higher probability of experience in the form of dreams or hallucinations.2,4 In both humans5,6 and rodent models, 7,8 interventions that raise acetylcholine concentration in the brain are associated with a reversal of anesthetic traits or a reduction in anesthetic potency. Conversely, lesions of cholinergic neurons in the basal forebrain—the main source of acetylcholine for the cortex —reduce anesthetic requirements for commonly used drugs such as isoflurane and propofol. 8,9