For the first time, UCLA scientists have identified the small group of brain cells believed to originate breathing in mammals. Reported in the September issue of Nature Neuroscience, their discovery could lead researchers to new approaches to addressing serious health problems, such as sleep apnea and sudden infant death syndrome.
In a previous study, the UCLA team had pinpointed a specific region of brain tissue called the preBotzinger Complex as the command post for controlling breathing in mammals. Now, within the region, they distinguished a small group of neurons responsible for issuing the commands that generate breathing.
“We hypothesized that if these neurons were important, something unusual would happen to breathing if we destroyed them,” said Dr. Jack Feldman, Edith Agnes Plum Professor, UCLA neurobiology chair and principal investigator. “As it turned out, we were right.”
Using a rat model, the UCLA team zeroed in on the roughly 600 neurons — less than one millionth of one percent of the total neurons in an adult rat’s brain. The researchers stained a unique marker on the cells’ surfaces to identify and count them. Then they administered a toxin that targeted the marker to kill just these cells.
The results proved striking in animals that lost more than 80 percent of their neurons.
“These rats’ breathing dissolved from a regular, rhythmic pattern into a highly irregular pattern of breathing frequency and depth,” said Dr. Paul Gray, UCLA neurobiologist and first author. “Equally important, the rats’ brains stopped controlling the amounts of oxygen and carbon dioxide in the bloodstream — the whole point of breathing,” he said.
While the findings prove the necessary role of these neurons in normal breathing, UCLA researchers are equally excited by the study’s implications for the future.
“Our findings suggest that these neurons may hold the underlying causes of breathing disorders and offer an excellent target for drugs treating these disorders,” Feldman said.
Because mammals’ brains are organized in similar ways, Feldman believes that the same portion of the human brain will likely control breathing as that of rats.
The UCLA team’s next step will be to locate the same set of neurons in a human brainstem and then compare their physiology and function with the neurons of people with breathing disorders. If his hypothesis proves correct, Feldman may find fewer or dysfunctional neurons in the brains of people with breathing disorders.
Funding was provided by the National Institutes of Health, a Ford Foundation Predoctoral Fellowship for Minorities and the Porter Physiology Development Program of the American Physiological Society. Drs. Wiktor Janzewski, Nicholas Mellen and Donald McCrimmon co-authored the study.
Journal
Nature Neuroscience