Carbon Dioxide Triggers Primordial Fear of Suffocation

The brain's fear center apparently has a built-in chemical sensor triggered by a primordial terror — threat of suffocation.

This discovery, which is based on studies of mice, could lead to ways to correct what goes wrong with people suffering from panic attacks. It could also shed light on why deep breaths can help calm people down.

Researchers focused on the amygdala, the part of the brain linked with both innate and learned fears. Past studies had revealed the so-called acid-sensing ion channel-1a (ASIC1a) is particularly abundant in the amygdala and the brain's other fear circuit structures, where it is required for normal responses in tests of fear behavior.

Scientists also know carbon dioxide reacts with water to form an acid — carbonic acid, the kind found in soft drinks. This, combined with the fact that rising carbon dioxide levels in the body herald suffocation, hinted that acidity might trigger fear by activating ASIC1a to warn the body of asphyxiation.

"The amygdala has been thought of as part of the fear circuitry of the brain," said researcher John Wemmie, a physician scientist at the University of Iowa at Iowa City. "Now we see it isn't just part of a circuit, it is also a sensor."

The scientists discovered that inhaling carbon dioxide increased brain acidity and evoked fear behavior in mice. Mice breathing 5 percent carbon dioxide — roughly 130 times higher than in normal air — tended to avoid open spaces more than usual.

In another experiment, mice experienced mild electrical shocks to their feet that taught them to fear a specific chamber. When these mice were shocked while in air containing 10 percent carbon dioxide, they displayed exaggerated freezing behaviors.

When the researchers disrupted the gene for the acid-sensing molecule in mice, they showed less fear in tests, a condition that was reversed when these compounds were generated specifically in the amygdala. Doses with bicarbonate to neutralize acidity reduced fear behaviors, while microinjections of acidified artificial cerebrospinal fluid into the amygdala did just the opposite.

The fact that the amygdala can both detect and respond to threats of suffocation makes sense, the researchers say.

"Detecting an elevated carbon dioxide is critical for survival," said researcher Michael Welsh at the University of Iowa. "When you are suffocating, this circuit triggers mechanisms for escape or relief of the problem."

For nearly a century, scientists have known that carbon dioxide inhalation can trigger panic attacks. People with panic disorder are particularly susceptible — a single breath of carbon dioxide can trigger panic attacks in them. Patients suffering from respiratory failure are also known to become extremely anxious.

"It has been proposed that panic and anxiety disorders involve a suffocation alarm gone haywire," Welsh said. "Now, this work may shed some light on this well-known phenomenon and suggests strategies for further exploration."

These studies in mice suggest that genetic variants in the acid-sensing process might predispose some individuals to anxiety disorders, including post-traumatic stress disorder.  If the findings bear out in humans, Wemmie suggested treatments that lower brain acidity could help, although he cautioned people shouldn't overdose on antacids to find out.

"In the shorter term, there's the possibility that one might be able to influence brain acidity with breath control," Wemmie told LiveScience. "Brain pH is very sensitive to breathing — if one breathes deeper for a time in a controlled way, one can actually reduce acidity."

A number of meditation techniques endeavor to instill calm through controlled breathing. "I wonder if some of those strategies came about and were developed over time recognizing the anxiety-lowering effects that ventilation can have," Wemmie added.

The scientists detailed their findings in the Nov. 25 issue of the journal Cell.

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