Central Hypoxia Elicits Long-Term Expression of the Lung Motor Pattern in Pre-metamorphic Lithobates Catesbeianus.

During vertebrate development, the neural networks underlying air-breathing undergo changes in connectivity and functionality, allowing lung ventilation to emerge. Yet, the factors regulating development of these critical homeostatic networks remain unresolved. In amphibians, air-breathing occurs sporadically prior to metamorphosis. However, in tadpoles of Lithobates catesbeianus (American bullfrog), hypoxia stimulates gill and lung ventilation during early development. Because accelerated metamorphosis is a useful strategy to escape deterioration of the milieu, we hypothesized that central hypoxia would elicit long-term expression of the lung motor command for air breathing in pre-metamorphic tadpoles (TK stages VI-XIII). To do this, we recorded respiratory activity from cranial nerves V and VII in isolated brainstems before, during, and up to 2 h after exposure to 15 min of mild (PwO2 range: 114-152 Torr) or moderate (PwO2 range: 38-76 Torr) hypoxia. To test for stage-dependent effects, data were compared between early (VI-IX) and mid (X-XIII) stages. Early stages responded strongly during moderate hypoxia with increased lung burst frequency (167%). Mild and moderate hypoxia increased lung burst frequency during the 2 h re-oxygenation period in early stage brainstems (136%, 497%, respectively), but produced only marginal effects on mid stage brainstems (39%, 31%, respectively). In contrast, hypoxia was not an important factor controlling fictive buccal burst frequency, which drives continuous gill ventilation in tadpoles prior to metamorphosis (all stages showed <25% increase). These preliminary results suggest that central hypoxia elicits long-term increases in lung burst frequency in a severity- and stage-dependent manner.