Emergence of air breathing in vertebrates

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BACKGROUND:    The transition from water to air breathing is arguably the most spectacular change in animal physiology. However, this transition requires significant transformations within the central nervous system that are still poorly documented. The long-term objective of my research program is to elucidate the neurological changes that contribute to the emergence of air breathing in vertebrates. Because they lie at the transition between water and air breathing, bullfrogs offer a unique animal model to explore this fascinating phenomenon. During my last NSERC granting term we tested the hypothesis that the endocrine and environmental signals regulating metamorphosis in frogs "reveal" the motor command driving lung ventilation. My trainees and I showed that hypoxia and thyroid hormones augment the occurrence of fictive air breaths in isolated brainstems from tadpoles. Our main objective over the next 5 years is to complete and expand this fruitful endeavour by evaluating the impacts of sex steroids on the motor command driving air breathing. RATIONALE:    Amphibians are the first vertebrates in which neurons located within the spinal cord are recruited to produce active expiration and assist lung ventilation. However, this is not observed in all species as the current data suggest that bullfrogs have lost this ability. However, the fact that frogs can recruit spinal neurons to produce mating calls brings us to reconsider this view. Since sex steroids are important for vocalisation and are powerful determinants of brain development we will test the hypothesis that elevation of sex steroids is necessary for the recruitment of spinal neurons to drive lung ventilation in bullfrogs. Here, experiments will be performed in adult frogs and developing tadpoles; the levels of androgens and estrogens will be manipulated experimentally in animals of both sexes. We will perform neuroanatomical tracing studies to evaluate the connectivity between spinal motoneurons and the parts of the brain that generate respiratory activity. These experiments will be complemented by electrophysiological studies to evaluate the impacts of selective activation/inhibition of target brain areas on respiratory activity. IMPACT OF RESEARCH AND TRAINING:    By the end of the next granting term, it is reasonable to anticipate that my trainees and I will have provided a comprehensive understanding of the neuroendocrine determinants of the emergence of air breathing in frogs. Our research will also shed new light on respiratory rhythmogenesis and the basic principles responsible for the production of active expiration. The potential impact of this work is significant: the recent interest for sex-based research has exposed our lack of knowledge on the contribution of sex hormones in respiratory neurobiology. As a whole, this research program will continue to provide trainees excellent opportunities to learn highly desirable skills in animal physiology and neuroscience.