A new study, published in the Journal of Neuroscience, identifies a group of neurons responsible for arousal that are directly triggered by carbon dioxide and cause mice to wake up without any changes to breathing.

Breathing too much carbon dioxide can happen during sleep if a particular sleeping position causes an obstructed airway or because of a medical condition like sleep apnea. Fortunately, inhaled carbon dioxide normally triggers sensitive brain mechanisms that prevent suffocation.

Researchers have long believed that inhaled carbon dioxide activates neurons responsible for breathing and the physical effect of increased deep breathing then triggers waking from sleep (arousal).

"Carbon dioxide-induced arousal is critical to diseases like sleep apnea and sudden infant death syndrome ( SIDS ), and is probably important in sudden unexpected death in epilepsy ( SUDEP ). not been well understood, "said Gordon Buchanan, assistant professor of neurology at the UI Carver College of Medicine.

"We show that neurons that should have nothing to do with breathing cause arousal from sleep when they are directly stimulated with carbon dioxide This represents a departure from the previous thinking and may change preventive management of these diseases where carbon dioxide-induced arousal plays a role. "

Previous research by Buchanan and his colleagues showed that serotonin (5-HT) neurons are important for carbon dioxide-induced arousal, because mice without serotonin neurons do not wake up when they inhale carbon dioxide.

However, there are two major groups of serotonin neurons: one in the midbrain involved in sleep-wake regulation and one in the medulla involved in the regulation of breathing. The new study separates the effects of these two groups of serotonin neurons.

The team showed that applying carbon dioxide-enriched artificial cerebrospinal fluid directly to the serotonin neurons in mice in an area of the midbrain known as the dorsal raphe nucleus (DRN) causes arousal from sleep. This arousal was lost if these midbrain serotonin neurons were blocked either by genetic manipulation or with chemical inhibitors.

Moreover, applying the carbon dioxide-enriched artificial cerebrospinal fluid directly to the serotonin neurons in the area of medulla increased breathing but did not cause arousal in mice.

"We propose that serotonin neurons in the DRN can be activated directly by carbon dioxide to cause waking independently of respiratory activation," says senior study author Buchanan.

"A better understanding of the mechanisms that underlie this protective reflex of waking up when too much carbon dioxide is inhaled might improve strategies for reducing death and disability caused by sleep apnea and SIDS ."

Carbon dioxide-induced arousal plays a role in both SIDS and sleep apnea, but in the case of SIDS, the arousal mechanism is thought to be impaired, while in the sleep apnea the arousal mechanism works well, but that leads to a host of secondary health problems

The study findings, "suggests that there should be ways to prevent apnea by maintaining normal carbon dioxide during sleep without causing arousal or to augment the arousal mechanisms in babies thought to be at a higher risk for SIDS." Similar approaches might also help prevent SUDEP, " Buchanan said.