New research from Seattle Children’s offers fresh insight into how the brain sets the pace of breathing.

Next time a workout has you winded, the inhibitory neurons in your brain may be to blame. This is according to new research from Seattle Children’s Research Institute that offers fresh insight into how the brain sets the pace of breathing.

In a study published in the journal Nature Communications, researchers used laser light to manipulate very specific classes of neurons responsible for breathing. The technique, known as optogenetics, helps scientists isolate neurons in the brain to study their function.

When stimulated in the lab, the researchers found excitatory neurons – the brain’s go signal – actually slow breathing, while inhibitory neurons – the brain’s stop signal – intervene to make breathing more rapid. In addition to explaining how the brain adapts breathing in response to everyday cues, the finding could lead to more precise treatments for neurological conditions that frequently involve breathing abnormalities.

Dr. Nino Ramirez, director of Seattle Children’s Center for Integrative Brain Research, oversaw the team of scientists leading the research.

“For the first time, it became clear how these two types of neurons work together to control breathing,” he said. “The counterintuitive discovery suggests that breathing disorders most likely occur when an imbalance of inhibition and excitation exists in the brain.”

Setting the pace of breathing

Inhibitory neurons in the breathing center of the brain shorten the time needed in between breaths, making breathing more rapid. Click image above to enlarge.

Breathing that adapts to changing environmental, metabolic and behavioral needs is essential to survival.

“A hallmark of breathing is that it is dynamic. It changes based on what our body needs,” Dr. Nathan Baertsch, a fellow in Ramirez’s lab, said. “Yet, exactly how the brain orchestrates such a wide range of breathing speeds remained unknown.”

To understand what causes changes in breathing rhythm, researchers looked at activity in the preBötzinger Complex (preBötC) – the breathing control center of the brain. About half of the neurons in the preBötC are inhibitory. Prior to this study, researchers did not completely understand their role in breathing.

“Excitatory neurons produce signals in the brain, causing inhalation. This is followed by a period of downtime before they repeat the process. In isolation, excitatory neurons result in very slow breathing that isn’t flexible,” Baertsch said.

It wasn’t until the researchers stimulated the inhibitory neurons that breathing picked up the pace.

“We found that the inhibitory neurons prevented the excitatory neurons from getting overexcited,” he said. “The time needed between inhalations shortened and breathing quickened.”

New techniques shed light on more precise treatments

Dr. Nino Ramirez studies breathing rhythms controlled by the brain in order to develop more precise treatments for neurological conditions that frequently involve breathing abnormalities.

By defining the mechanisms in the brain that control breathing, scientists can pinpoint what goes wrong in neurological disorders that cause significant disruption to normal breathing rhythm.

Children with Rett syndrome, epilepsy and other central nervous system disorders commonly experience erratic breathing. Current treatments for these conditions offer limited effectiveness because they do not target the neurons responsible for the neurological symptoms. According to Ramirez, finding better therapies starts with identifying the root cause of the symptoms – a once impossible task now made possible through techniques such as optogenetics.

“It is very difficult to predict how neurons cause neurological disorders without interrogating them in a specific manner,” Ramirez said. “New techniques allow us to study the brain and nervous system with a degree of specificity not possible before.”

He hopes that insights gained from using more specific approaches will lead to more precise treatments for neurological disorders.

“Eventually, precise approaches will replace generic, relatively unspecific treatments to manage a wide spectrum of neurological disorders ranging from epilepsy to Parkinson’s disease,” he said.

 

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