How wakefulness is generated by the brain?

What is it about?

Staying awake is often thought to rely on a few well-known brain systems, particularly those using chemicals like dopamine, serotonin, or orexin. However, this study shows that the picture is more complex. We examined brain activity across the whole brain in mice to compare how wakefulness is produced in three situations: naturally, and under the effects of two wake-promoting drugs, modafinil and solriamfetol. Using a technique that labels recently active neurons, we identified which brain regions were involved in each case. We found that some brain areas were consistently active regardless of how wakefulness was induced. These included orexin neurons and regions in the brainstem known to support alertness, suggesting a shared “core” wake network. Surprisingly, other regions—many not previously linked to wakefulness—were much more strongly activated by solriamfetol than by modafinil or natural waking. These areas are located in deeper parts of the brain involved in stress, autonomic regulation, and internal body signals. In contrast, several classic wake-related systems, such as certain dopamine, serotonin, and noradrenaline neurons, were only weakly activated or not prominently involved.

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Photo by 光术 山影 on Unsplash

Photo by 光术 山影 on Unsplash

Why is it important?

Overall, our results suggest that different types of wakefulness rely on partly distinct brain circuits, depending on how they are triggered. This could help explain why wake-promoting drugs have different effects and may lead to improved treatments for disorders like narcolepsy and excessive sleepiness in sleep apnea.

Perspectives