New Brain Research Explains the Elusive Neurons of Brain That Control Breathing

Los Angeles, CA, Oct. 5 – Breathing is the most important function of a body. On average, a person breathes at least 20,000 times a day, and it happens automatically without consciously thinking about it.

A respiratory control system at the core of our brain controls a complex breathing system. Sensors in the brain send signals down to the spine, muscles and lungs, instructing them to change breathing requirements and oxygen levels. These sensors in the brain take data about the required oxygen levels from the blood vessels and accordingly adjust the breathing rhythm. For the most part, breathing is automatic, inexplicably controlled by sensors in the brain and to a limited degree; a person can also consciously control the breathing rhythm. Our body automatically adjusts to different breathing needs, such as during swimming, running, when we get angry or scared.

Breathing is essential for life, and any disturbance in the breathing system can be fatal. In a worst-case scenario, it can lead to death with sudden death syndrome (SDS). If brain sensors that detect oxygen levels in the blood malfunction or stop working, a person can suffer from breathing diseases, chronic sickness, and these situations lead to serious health consequences. Also, people fall short of breath with Asthma or breathing is interrupted during sleep with sleep apnea disorder.

According to the National Institutes of Health, a respiratory disease Chronic Obstructive Pulmonary Disease (COPD) is the third leading cause of death in the United States. Diseases and conditions that impair breathing can cause respiratory failure. In a medical case, an 8-year-old Luton boy was diagnosed with a rare genetic disorder called Congenital Central Hypoventilation (CCHS). His body forgets to breathe when he concentrates for long periods. This rare case sheds ample light on the complexity of the mechanisms by which the brain regulates breathing. There are many things we know about the respiratory system, but there is a lot to learn on exactly how neurons in the brain signal and control our breathing system.

Twenty-five years ago, scientists discovered a network of neurons in the brainstem that controls rhythmic inhalation, called the pre-Bötzinger complex (pre-BötC). However, how exactly the pre-BötC neurons signal and generate the breathing rhythm remained elusive. It took scientists almost two decades to hypothesize that brain neurons generate two distinct signals; one is responsible for the respiratory rhythm and the other controls the pattern. Advancing these important studies, distinguished professor Jack Feldman’s group at UCLA dissected the neural microcircuits that control breathing and elucidated the functional role of pre-BötC neurons.

In this research, Dr. Yan Cui et al. dissected the neural microcircuits that control breathing and elucidated the functional role of the neurons in pre-BötC. The study uncovered the functionally distinct, rhythm and pattern generating pre-BötC microcircuits. The research highlights that Dbx1⁺ neurons in pre-BötC control the respiratory rhythm and Dbx1⁺ and SST⁺ neurons shape the output pattern. Moreover, SST⁺ neurons mediate pathways and these two types of neurons within pre-BötC control the whole breathing system through distinct signals. These findings are significant to understand the functional roles of the neurons inhibiting in the pre-BötC that distinctly control the rhythm and pattern of breathing. The findings provide the foundation for testable models with the potential to provide a clear understanding of breathing.

Current neural models of the circuits underlying respiratory rhythm generation are hampered by an absence of unequivocal experimental data supporting their often stipulated connectivity. Most of the anatomical studies have been limited to some areas of the brain, and functional studies based on cross-correlations have not been supported by sufficient data essential to conduct meaningful tests. This advancement in understanding the anatomical and functional data of microcircuits will open up new possibilities of constructing explicit computational models with realistic constraints on connectivity.

By deciphering the functional circuits of the brain, this study can lead to significant advancements in understanding the brain diseases that affect breathing or sleep apnea. It would help scientists to understand the mysterious breathing disorders, such as Congenital Central Hypoventilation (CCHS) or sudden death due to breathlessness. The computational models that can be designed using this data will be instrumental in understanding the cross-correlation of the segregated regions of the brain. It could be useful for researching potential new ways to save lives with a deeper understanding of how brain functions and controls breathing.

More information: Yan Cui et al. Defining preBötzinger Complex Rhythm- and Pattern-Generating Neural Microcircuits In Vivo, Neuron (2016). DOI: 10.1016/j.neuron.2016.07.003