Escape From Oblivion: Neural Mechanisms of Emergence From General Anesthesia

Abstract

The question of how general anesthetics suppress consciousness has persisted since the mid-19th century, but it is only relatively recently that the field has turned its focus to a systematic understanding of emergence. Once assumed to be a purely passive process, spontaneously occurring as residual levels of anesthetics dwindle below a critical value, emergence from general anesthesia has been reconsidered as an active and controllable process. Emergence is driven by mechanisms that can be distinct from entry to the anesthetized state. In this narrative review, we focus on the burgeoning scientific understanding of anesthetic emergence, summarizing current knowledge of the neurotransmitter, neuromodulators, and neuronal groups that prime the brain as it prepares for its journey back from oblivion. We also review evidence for possible strategies that may actively bias the brain back toward the wakeful state.

Figure 1.

As in the human, the cholinergic system in the rodent brain arises from brainstem laterodorsal tegmental (LDT) and pedunculopontine tegmental (PPT) nuclei shown in green as well as from basal forebrain sites shown in purple. Reprinted from Behavioural Brain Research, 221, Woolf NJ, Butcher LL, “Cholinergic Systems Mediate Action From Movement to Higher Consciousness,” 488–498, 2011, with permission from Elsevier. bas indicates nucleus basalis; BLA, basolateral amygdala; DR, dorsal raphe; EC, entorhinal cortex; hdb, horizontal diagonal band nucleus; ICj, islands of Cajella; IPN, interpeduncular nucleus; LC, locus coeruleus; LH, lateral hypothalamus; ms, medial septal nucleus; si, substantia innominata; SN, substantia nigra; vdb, vertical diagonal band nucleus.

Figure 2.

As in the human, adrenergic neurons arising from the pons and medulla project both rostrally toward the midbrain and forebrain (f.brain) and caudally toward the spinal cord. The largest collection of adrenergic neurons is found in the locus coeruleus (LC). Figure modified from Holloway et al. cereb indicates cerebellum; hippo, hippocampus; olf, olfactory.

Figure 3.

As in the human, the orexin/ hypocretin system in the rodent brain arises from a small number of neurons found only in the lateral, perifornical, and posterior hypothalamus (shown in purple) but projects widely throughout the neuroaxis. Reprinted from Trends in Neurosciences, 23, Kilduff TS, Peyron C, “The Hypocretin/Orexin Ligand-Receptor System: Implications for Sleep and Sleep Disorders,” 359–365, 2000, with permission from Elsevier.