Phylogeny of vertebrate respiratory rhythm generators: the Oscillator Homology Hypothesis

A revolution is underway in our understanding of respiratory rhythm generation in mammals. Until recently, a major focus of research within the field has centered around the question of locating and elucidating the mechanism of rhythmogenesis of a single respiratory neuronal oscillator which is reiterated bilaterally within the brainstem. Now it appears that each hemisection may contain at least two oscillators that interact to generate the respiratory rhythm in mammals. Comparative studies have hinted at the existence of multiple respiratory oscillators in non-mammalian vertebrates for some time, raising the possibility of homologous oscillators. Here, we consider available tools to identify neuronal oscillators and critically review the evidence for the importance and existence of multiple respiratory oscillators in vertebrates. First focusing on a comparison between frogs and mammals, we then evaluate the hypothesis that ventilatory oscillators in extant tetrapods evolved from ancestral oscillators present in fish (the Oscillator Homology Hypothesis). While supporting data are incomplete, the Oscillator Homology Hypothesis will likely serve as a useful framework to motivate further studies of respiratory rhythm generation in lower vertebrates.