By Aadit Tambe
Scientists long believed that carbon dioxide inhaled during sleep activates neurons responsible for breathing and causes a person to wake up.
However, a recent University of Iowa study 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, according to a press release from the Carver College of Medicine.
“Arousal from sleep is important because it wakes the person up and restores tone to the airway, so it allows normal flow of air,” senior study author and Assistant Professor of neurology Gordon Buchanan said. “Without that, the person would remain obstructed and die.”
The study indicates that arousal from sleep in response to increased carbon dioxide can occur independent of breathing, research assistant and coauthor Callie Ginapp said in an email to The Daily Iowan.
This is especially relevant in the case of sudden infant death syndrome and sudden unexpected death in epilepsy, she said
This means specific pathways in the brain could be targeted to restore arousal to increase carbon dioxide in patients who have malfunctioning arousal responses, as is thought to occur in the two syndromes, Buchanan said.
Although many others are working on studies on similar topics, this is the first one of its kind, he said.
“We hypothesized that you don’t need the big increase in breathing, and you can actually activate groups of neurons that regulate arousal directly with [carbon dioxide] without causing increase in breathing,” Buchanan said.
Previous studies have shown that if certain brain signaling molecules called serotonin are eliminated, arousal from sleep because of carbon dioxide can be prevented.
There are two populations of serotonin neurons in the brain, the first being those that regulate breathing and were thought to regulate arousal. However, there is a second population of serotonin in the midbrain that is involved in arousal, Buchanan said.
This study focused on showing that if the second population was activated, without the first being activated, arousal from sleep can ensue, he said.
Three different types of genetically modified mice were used to hone in on the question of which population of neurons are specifically involved in arousal.
“We used mice because it is easy to isolate [specific questions] in animal models than in people,” he said. “The hope is that we would be able to translate the animal work to patients.”
The arousal from sleep is needed to restore tone to the airway and is lifesaving in case of sleep apnea. If this is not regulated, people may not wake up.
Buchanan and his team think that people who die from sudden infant death and sudden death in epilepsy have a dysfunctional arousal system.
“If you consider babies [who] get put on their face, they will rebreathe [carbon dioxide],” Buchanan said. “This will wake them up because they will cry, and this will prevent breathing [carbon dioxide].
“If they have dysfunctional [carbon dioxide] arousal system, they won’t wake up and [will die because of] rebreathing [carbon dioxide].”
The next step will be to try to restore airways to patients with sleep apnea without causing arousal for patients who are at high risk of sudden infant death and sudden death in epilepsy so that they are not affected by this dysfunction, Buchanan said.
“This study represents a paradigm shift in the way that we think about an important neurotransmitter, serotonin,” Benton Purnell, a coauthor of the study, said in an email to the DI.
“Fifty years ago, we knew that serotonin was important in sleep-wake regulation, but everyone believed that it was a critical sleep-promoting agent,” he said. “Now we know that the inverse is closer to true — serotonin promotes wakefulness.”