Newfound brain microcircuit is critical for breathing control

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Newfound brain microcircuit is critical for breathing control

Recently located cell network couples rhythmically with related brain-stem regions to choreograph respirations
Leila Gray

Researchers have discovered a brain-cell network that drives a respiratory phase important for the control of exhalation.

This phase, also called postinspiration, occurs after air is inhaled.

Within the brainstem, distinct populations of cells produce and choreograph the timing of impulses sent to different muscles involved in breathing.  A rhythm is established that keeps air flowing in and out of the lungs. 

Where this new network is located, and how it might be coupled with brain-stem regions that control the other phases of the breathing cycle, are reported this week in Nature. 

Tatiana Anderson
Project lead and UW Ph.D. candidate Tatiana Anderson
Project lead and UW Ph.D. candidate Tatiana Anderson

The findings were made by researchers from the Center for Integrative Brain Research at Seattle Children’s Research Institute, the University of Washington School of Medicine’s departments of pediatrics and neurological surgery, and the UW Graduate Program in Neuroscience.

The leads on the project team were UW Ph.D. student Tatiana M. Anderson and postdoctoral fellow Alfredo Garcia III, now an assistant professor at the University of Chicago. The senior investigator was Jan-Marino Ramirez, UW professor of neurological surgery.

The scientists wanted to better understand the brain’s control of postinspiration, because without it we would struggle to talk, cough, sneeze and swallow, as these must be worked around air intake.  

In their later stages, several brain-damaging diseases such as Alzheimer’s and Parkinson’s upset the coordination of inspiration and postinspiration.  Aspiration pneumonia and choking are major causes of death in the elderly.  Problems with the brain not smoothly operating breathing phases might also cause long pauses in breathing known as apnea.

In this study, the researchers found a population of cells that were specifically active during postinspiration.  The researchers referred to this newly uncovered network as PiCo, for postinspiration complex.

The PiCo brain cells can release both acetylcholine and glutamate, both of which can modulate nerve networks. 

Jan-Marino Ramirez
Seattle Children's
UW Medicine neurological researcher Jan-Marino Ramirez directs the Center for Integrative Brain Research at the Seattle Children’s Research Institute.
picture of UW Medicine neurological researcher Jan-Marino Ramirez, who directs the Center for Integrative Brain Research at the Seattle Children’s Research Institute.

The PiCo neurons were also sensitive to opioids and somatostatin. Their sensitivity is consistent with the way these drugs interfere with breathing.

The researchers observed the rhythm-generating properties in the PiCo.   Its timing was such that its cells discharged immediately after the cell populations that managed inspiration.  Details of the latest study provided evidence that the glutamatergic/cholinergic brain cells within the PiCo network were important for rhythm generation. 

Based on their results, the researchers proposed a triple oscillator model of breathing regulation: Three microcircuits located in spatially distinct areas of the brain manage different phases of the cycle in a coordinated fashion.

The presence of three discrete networks, the researchers suggested, might make it easier to differentiate the control of behaviors that need to coincide with breathing.  This type of nerve cell multi-network organization for generating rhythmical signals may be more widespread in nature.  It allows for flexible control, they noted, of complex biological activities, like locomotion or scratching.

The research was supported by grants from the National Institutes of Health.
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