Do we really know how we breathe?

I tried to put together a more readable version of a previous post about the neural control of breathing.

Breathing is the most conspicuous rhythmic behavior of humans, it consists of repeating the cycle of inspiration, postinspiration (a phase in which the muscle contraction achieved by the inspiratory phase is upheld) and expiration. The neural structures responsible for these processes are well known, they are localized in the brainstem. However, the concrete mechanism by which these collections of neurons instantiate breathing is not yet known. There are of course several models which attempt to explain how these neurons generate the rhythmic activity patterns required for the contractions of the muscles of breathing.

The first model emerged in the 70’s and proposed that activity spontaneously rises in one group of cells and this generates inspiration. When the activity reaches a certain limit, it brings into action an inhibitory system. This system inhibits activity in the inspiratory neurons, and thus the inspiratory muscles relax and expiration occurs. Even in its earliest form, the model could explain the activity pattern seen in the nerve controlling the inspiratory muscles, however experimental data suggests that inhibitory neurotransmitters have no significant effect on the respiratory cycle. In the early 90’s researchers found pacemaker cells in the brainstem respiratory area in brain slices from rats. Pacemaker cells have the ability to generate a rhythmic activity pattern without any input from other neurons (their special ion channels enable this), but such cells have never been identified in the respiratory center of live animals, which makes this explanation unlikely. The most likely model is the network oscillator, which appeared in the 2000s. The idea is that some of the cells become spontaneously active and excite their neighbors, then those neighbors excite their neighbors and so on. Finally this collective activity culminates in a refractory period, during which neural activity is inhibited by the ion currents, generated by the increased activity beforehand. Thus, this model does not involve inhibitory neurotransmission or pacemaker cells to explain the generation of the rhythmic neural activity required for breathing.

File:2327 Respiratory Centers of the Brain.jpg
A visual representation of the classic activation-inhibition model By OpenStax College [CC BY 3.0 (https://creativecommons.org/licenses/by/3.0)%5D, via Wikimedia Commons

The network oscillator model may be the most likely explanation of breathing, however it still leaves out several important factors which should be considered for a complete elucidation. For example, some results suggest that high frequency neural activity may not be needed for rhythm generation, but most models presuppose this requirement. Glial cells may have an important role in the process, but none of the current models consider them. Finally, the models are based on rodent physiology and the respiratory rhythm is much faster in these mammals (2-5/sec) than in humans (12-18/min). It is not sure that the same mechanism can generate such different rhythms. All this points to the fact that the neural control of breathing is beyond current understanding, even though it is probably one of the simpler functions of the nervous system.

Resources:

Breathing matters” – Nature Reviews Neuroscience

This is a refined version of a previous post – “The neural basis of breathing”