Breathing and the Brainstem

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Neuroscience researchers at Seattle Children’s made an unusual discovery in 2016: an uncharted area of the brain necessary to breathing.

In 2016, neuroscience researchers at Seattle Children’s Research Institute made an unusual discovery: another area of the brain essential to a basic human function.

“It has been 25 years since scientists found the part of the brain essential for breathing,” says Dr. Nino Ramirez, who leads Seattle Children’s Center for Integrative Brain Research. “Discovering another brain area involved in this essential function was unexpected.”

And PiCo makes three

Scientists discovered a network of neurons in the brainstem that controls rhythmic inspiration (known as the pre-Bötzinger complex) in 1991. More recently, researchers determined active expiration was generated within the lateral parafacial region of the brain.

In the August 2016 edition of Nature, the Seattle Children’s team described a network of neurons that are active during passive exhalation and therefore important to behaviors that follow inhalation, such as swallowing, speaking and coughing. The team named this network the postinspiratory complex, or PiCo. The team also found that PiCo establishes the timing and coordination of inspiration and postinspiration.

“A person can develop life-threatening complications if the inhalation and exhalation phases of breathing are not coordinated.”
– Dr. Nino Ramirez

“This is a clinically important finding because a person can develop life-threatening complications if the inhalation and exhalation phases of breathing are not coordinated,” says Ramirez. “Patients with neurodegenerative conditions like Parkinson’s disease or Alzheimer’s disease frequently develop aspiration pneumonia because their breathing may be uncoordinated when they eat.”

New researcher makes her mark

The research team for this groundbreaking discovery was led by Tatiana Anderson, a doctoral candidate in neuroscience from the University of Washington. While it’s not uncommon for graduate students to work on large research projects, it is unusual for a graduate student to be the lead author on such a major discovery.

“Our graduate students and post-doctoral fellows are the researchers of the future,” says Ramirez. “When they come to work at Seattle Children’s, we want to give them real-life research experience and the confidence to take the lead and probe further, ask questions and step outside of the box. That’s how discoveries like this are made.”

Getting to know PiCo

“Our next steps are to look more carefully at how the neurons in this PiCo region of the brain operate,” says Ramirez. “We want to find out things like whether these neurons are reduced or not functioning properly in patients with neurodegenerative diseases.”

“Perhaps we can identify drugs or other therapies that can target these neurons and make them function as they’re supposed to,” adds Anderson.

The discovery of the PiCo region could also shed light on respiratory complications related to drug overdoses.

“We found that PiCo is extremely sensitive to opiates, which could help explain why people who overdose have slurred speech and sometimes develop aspiration pneumonia,” says Anderson.

Further study of PiCo may also advance understanding of sudden infant death syndrome (SIDS), which is thought to be linked to abnormalities in breathing and arousal.

“We’re very excited to have found a part of the brain that is such a vital part of a basic human function,” says Ramirez. “We are going to keep pursuing this promising line of research in the hopes of improving and saving lives.”

Published in the Academic Annual Report, March 2016