As grateful patients can attest, anesthesia lets people sleep through even the most drastic of operations. Now a study shows how a common type of anesthetic sends the brain to slumberland. The finding, reported online 26 August in Nature Neuroscience, could lead to new drugs with lower chances of side effects.
Some of the most widely used anesthetics act on receptors for the neurotransmitter GABA, a small molecule used primarily as an ‘off' switch by the brain. These so-called GABAergic anesthetics create something similar to non-REM sleep, the dark gulfs of inactivity between dreams. This type of sleep is thought to be triggered when the brain produces GABA to shut down a clump of neurons known as the tuberomammillary nucleus (TMN). The sleep-inducing TMN was suspected to be the prime target of the GABAergic anesthetics.
To test this idea, neuroscientist Nick Franks and colleagues at Imperial College, London, anesthetized mice in various ways. Before administering GABAergic anesthesia, they injected a drug called gabazine into the TMN. Gabazine blocks GABA and similar molecules from receptors, thus preventing the deactivation of neurons. As predicted, GABAergic anesthetics could not knock out the mice treated with gabazine. But when mice were knocked out with ketamine, a non-GABAergic anesthetic, they slept soundly with or without the injection of gabazine. This reveals that the TMN is a direct target of the GABAergic anesthetics, establishing a link between anesthesia and the brain's natural path to sleep.
The results impress Neil Harrison of Cornell University because they bridge the fields of anesthesia and neurophysiology. All general anesthetics pose a small health risk to patients, he says, but with this new insight, scientists may now be able to design drugs that render patients unconscious without the risk of upsetting their breathing or blood pressure.