Pre-Bötzinger Complex

The Pre-Bötzinger Complex (Pre-BötC) is a small area in the medulla oblongata of the brainstem that is crucially involved in generating the rhythm of breathing^[1].

It was identified in the early 1990s by a team led by Jack L. Feldman and Jeffrey C. Smith of UCLA^[2], and has since been the focus of much research in the field of respiratory physiology. You can listen to a 4 minute clip of Prof. Jack Feldman speaking to the BBC about the naming of the Pre-Botc in this clip (unfortunately, it doesn't embed).

The Pre-BötC is primarily comprised of a network of interneurons. These neurons are thought to contain special pacemaker properties that allow them to generate rhythmic neural activity^[4]. This rhythmic activity is ultimately transmitted to the motor neurons that innervate the diaphragm and other muscles of respiration, resulting in the rhythmic muscle contractions and relaxations that constitute breathing^[5].

Researchers have divided these interneurons into different subtypes based on their neurochemical properties and the specific roles they play in respiratory rhythmogenesis^[7]:

1. Inspiratory neurons: These neurons fire action potentials during inspiration, driving the contraction of inspiratory muscles like the diaphragm. Their activity is thought to underlie the basic rhythm of breathing.

2. Expiratory neurons: These neurons become active during forced exhalation (like during exercise or coughing), driving the contraction of expiratory muscles.

3. Pacemaker neurons: These neurons possess intrinsic pacemaker properties that allow them to generate rhythmic activity even when isolated from the rest of the network. The mechanisms that confer these pacemaker properties are still a subject of ongoing research, but they are thought to involve persistent sodium currents and calcium-activated non-selective cation currents.

The Pre-BötC also contains inhibitory and excitatory neurons that modulate the activity of the inspiratory and expiratory neurons, adjusting the respiratory rhythm based on the body's needs^[8]. For example, during physical exercise, excitatory input to the Pre-BötC might increase to speed up the respiratory rhythm and match the body's increased demand for oxygen^[9].

The Pre-BötC is connected to other areas of the brainstem involved in respiratory control, such as the parafacial respiratory group and the Bötzinger complex, which further modulate its activity^[10].

Despite being a relatively small part of the brain, the Pre-BötC is critical for life. Damage to or dysfunction of this area can lead to severe breathing difficulties or even cessation of breathing, which is why it is a key area of study for understanding and treating respiratory disorders.