Emergence of air breathing in vertebrates

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The transition from water to air breathing is arguably the most spectacular change in animal physiology. Given the substantial differences in physico-chemical properties between water and air, a successful transition in respiratory medium requires significant transformations in the neural circuits that generate and regulate breathing. Using the American bullfrog (Lithobates catesbeianus) as our main model system, the long term objective of my research program is to understand the neurophysiological changes within the respiratory control system associated with the emergence of air breathing in vertebrates. During early life, tadpoles ventilate their gills by producing a continuous, high frequency, low amplitude activation of the buccal pump. As the lungs develop, a more forceful but less frequent activation of the buccal pump emerges progressively to push air into the lungs. Experiments performed on isolated brainstems (in vitro) from pre-metamorphic tadpoles show that the circuits driving lung ventilation are present well before air breathing contributes to gas exchange but is inhibited. In light of the evidence indicating that expression of the motor command producing lung ventilation is highly plastic, we propose to combine electrophysiological studies (isolated brainstem preparation, whole cell recording with patch clamp) with whole animal measurements of respiratory activity (in vivo) to address the following specific aims: 1) The electrical properties and morphology of trigeminal motoneurons undergo significant changes during development. 2) Developmental changes in acid-base status contribute to the emergence of air breathing. 3) Thyroid hormone (TH) facilitates the expression of air breathing in pre-metamorphic tadpoles. 4) Brainstem hypoxia is sufficient to facilitate expression of air breathing in pre-metamorphic tadpoles. The research proposed for the next grant cycle is an important milestone in my research program and the outcome will advance basic knowledge in respiratory neurobiology. By combining simple experiments with “state of the art” electrophysiological approaches, this program will help trainees acquire basic expertise in research as well as highly desirable skills regardless of the stage of their academic training.