Penn Medicine Basic and Translational Research
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Going to Sleep vs. Going Under

One way to determine the similarities or differences between sleep and general anesthesia is to determine whether they're interchangeable in function -- in this case, can anesthetically induced unconsciousness substitute for natural sleep? At least in an animal model, the answer is partially, discovered Max Kelz, MD, PhD, associate professor of Anesthesiology and Critical Care. Monitoring anesthetized mice for REM and non-REM (NREM) sleep, Kelz found that inhaled anesthetics strongly inhibited REM sleep, with the animals incurring a substantial REM sleep deficit that needed to be made up after the anesthesia. However several anesthetics did appear to partially substitute for NREM sleep as no NREM sleep debt accrued after a prolonged state of anesthesia.

Another study by Kelz's research group showed that at least one common anesthetic, isoflurane, works by actually "hijacking" the brain's natural sleep circuitry by directly activating sleep-producing neurons in the hypothalamus. Animals that lacked proper function of those specific neurons showed marked resistance to the drug.

Kelz's research continues to probe deeper into the workings of anesthesia and its relationship to sleep. The team recently reported that by manipulating four genes known to be involved in natural sleep, the brain's "neural inertia" that resists the transition from wakefulness to an anesthetic state can be controlled. They also found that the process of "going under" is substantially different from "waking up" from general anesthesia, and that different anesthetic drugs work on different neural pathways. Similarities between neural inertia and sleep inertia, in which a return to full cognitive awareness is delayed after natural sleep, may reveal some important clues as to how different drugs work and how to avoid some of their harmful side effects.