Is the vertebrate respiratory central pattern generator conserved? Insights from in-vitro and in-vivo amphibian models.

There have been considerable advances in our understanding of the anatomical substrates, neural connections and modulation of the mammalian respiratory central pattern generator (CPG). Despite these advances, however, relatively little is known about the regulation of CPGs for breathing in other vertebrates. It has been proposed that CPGs supporting a variety of motor behaviors such as breathing, locomotion, scratching and chewing, have been conserved in the course of vertebrate evolution. 14, 15 At present, there is little experimental support for this hypothesis. At first glance it would appear that breathing in ‘lower’ vertebrates, such as amphibians, and mammals have little in common save for the use of lungs for gas exchange. Amphibians use a positive-pressure, buccal force pump to inflate the lungs in contrast to the negative-pressure, aspiratory lung inflation mechanism present in mammals and other amniotes (birds and reptiles). In amphibians, the primary respiratory muscles responsible for generating airflow during breathing are innervated by cranial nerves, whereas in mammals the cranial nerves innervate muscles associated primarily with control of the upper airway. During the course of evolution the diaphragm, intercostals and abdominal muscles, which are innervated by spinal nerves, have assumed the role of the ‘power plant’ for generating airflow during breathing. Despite these obvious differences in the mechanical aspects breathing, it is generally agreed that the peripheral structures associated with breathing are far less constrained by evolutionary change than the neural structures that support and control the peripheral elements. In other words, CPGs, in general, appear to be much more conserved than the structures with which they control. Direct evidence for conserved features of the respiratory CPG is sparse in vertebrates, but there are numerous examples of invertebrate