Three paired groups of respiratory nuclei are oriented more or less in columns in the pontine and medullary tegmentum (Fig. 25-8). They comprise (1) a ventral respiratory group (referred to as VRG), extending from the lower to the upper ventral medulla, in the region of the nucleus retroambiguus; (2) a dorsal medullary respiratory group (DRG), located dorsal to the obex and immediately ventromedial to the NTS; and (3) two clusters of cells in the dorsolateral pons in the region of the parabrachial nucleus. From electrical-stimulation experiments, it appears that paired neurons in the dorsal pons may act as “on–off” switches in the transition between inspiration and expiration.
Inspiratory neurons are concentrated in the dorsal respiratory group and in the rostral portions of the ventral group, some of which have monosynaptic connections to the motor neurons of the phrenic nerves and the nerves to the intercostal muscles. Normal breathing is actively inspiratory and only passively expiratory; however, under some circumstances of increased respiratory drive, the internal intercostal muscles and abdominal muscles actively expel air. The expiratory neurons that mediate this activity are concentrated in the caudal portions of the ventral respiratory group and in the most rostral parts of the dorsal group. On the basis of both neuroanatomic tracer and physiologic studies, it has been determined that these expiratory neurons project to spinal motor neurons and have an inhibitory influence on inspiratory neurons.
The pathway of descending fibers that arises in the inspiratory neurons and terminates on phrenic nerve motor neurons lies just lateral to the anterior horns of the upper cervical cord segments. When these tracts are damaged, automatic but not voluntary diaphragmatic movement is lost. As noted later, the fibers carrying voluntary motor impulses to the diaphragm course more dorsally in the cord. The phrenic motor neurons form a thin column in the medial parts of the ventral horns, extending from the third through fifth cervical cord segments. Damage to these neurons, of course, precludes both voluntary and automatic breathing.
As mentioned, the exact locus from which the breathing rhythm is generated, if there is such a site, is not known. The conventional understanding has been that the DRG was the dominant generator of the respiratory rhythm but the situation is certainly more complex. Animal experiments have focused attention instead on the rostral ventrolateral medulla (VRG). This region contains a group of neurons in the vicinity of the “Botzinger complex” (which itself contains neurons that fire mainly during expiration). Cooling of this area or injection with neurotoxins in animals causes the respiratory rhythm to cease (see the review by Duffin et al). It has also been shown that the paired respiratory nuclei in the pons that are thought to act as switches between inspiration and expiration possess a degree of autonomous rhythmicity but their role in engendering cyclic breathing has not been clarified. Some workers are of the opinion that two or more sets of neurons in the VRG create a rhythm by their reciprocal activity or that oscillations arise within even larger networks (see Blessing for details).
There are also centers in the pons that do not generate respiratory rhythms but may, under extreme circumstances, greatly influence them. One pontine group, the “pneumotaxic center,” modulates the response to hypoxia, hypocapnia, and lung inflation. In general, expiratory neurons are located laterally and inspiratory neurons medially in this center, but there is an additional group that lies between them and remains active during the transition between respiratory phases. Also found in the lower pons is a group of neurons that prevent unrestrained activity of the medullary inspiratory neurons (“apneustic center”). In addition to these ambiguities regarding a “center” for the generation of respiratory rhythm, there is the difficulty that the nuclei described earlier are not well defined in humans.