Sleep and Anesthesia Have Different Neural Mechanisms

Post by Anastasia Sares

What's the science?

We have been using general anesthetics for over 150 years, but how they work is still a mystery. One hypothesis is that anesthetics hijack the body’s sleep-wake mechanism, an intuitive assumption since being under anesthesia feels a lot like falling asleep. However, this week in Current Biology, Vanini and colleagues showed that manipulating the activity in brain areas controlling the sleep-wake cycle did not change the effects of anesthesia.

How did they do it?

The authors used mice with precise genetic modifications (induced with Cre-Lox) so that they could selectively target excitatory (glutamatergic) and inhibitory (GABAergic) neurons in the preoptic region of the brain. This preoptic region is known to be involved in sleep-wake cycles. After their preoptic region was either excited or inhibited, the mice were administered different levels of isoflurane, an anesthetic. The authors timed how long it took them to lose consciousness, and how long it took to regain consciousness again. In a separate group of mice, the authors performed the same manipulation, but instead of putting the animals under anesthesia, they monitored their sleep-wake cycles using brain (EEG) and muscle (EMG) recordings.

What did they find?

All of the groups of mice that received anesthesia had a similar timeline for losing and regaining consciousness: it didn’t matter whether the sleep-wake area of the brain had been activated or inhibited. The authors interpreted this to mean that the anesthesia was not interacting with the sleep-wake cycle, and was instead causing a loss of consciousness by other means. The manipulation did affect the sleep-wake cycles of the mice, as would be expected.

What's the impact?

Previous work seemed to show that anesthesia and sleep were linked, but most of this data was correlational. The direct manipulations used here had the potential to establish a causal link between these two processes and failed to find one, demonstrating once again that correlation does not equal causation. This brings up a lot of questions about how the loss of consciousness under anesthesia could be different from sleep. Knowing how anesthesia works might help us find ways to improve its medical use.

Vanini et al. Activation of preoptic GABAergic or glutamatergic neurons modulates sleep-wake architecture, but not anesthetic state transitions. Current Biology (2020). Access the original scientific publication here.