Stimulating a population of neurons in the midbrain with carbon dioxide (CO2) awakens adult male mice without enhancing breathing. These findings, published in the Journal of Neuroscience, are relevant to understanding disorders such as obstructive sleep apnea, sudden infant death syndrome, and sudden unexpected death in epilepsy.

Rising levels of CO2 trigger the drive to breathe, and cause arousal from sleep. Disorders that interfere with this important signal can disrupt sleep and, in some cases, lead to death. The mechanism by which CO2 causes arousal from sleep—a reflex critical to survival—is not well understood.

Gordon Buchanan and colleagues demonstrate that activation of serotonin neurons in the midbrain dorsal raphe nucleus (DRN) with CO2-saturated, artificial cerebrospinal fluid woke up sleeping mice. Activation of similar neurons in the medulla, on the other hand, increased breathing but did not wake the mice up. The study identifies a direct pathway through which CO2 induces arousal independent of changes in breathing.