When early developmental stage tadpoles are denied access to the air- water interface to take lung breaths, metamorphosis is arrested in spite of adequate temperature, food, oxygen, and photoperiod. The developmental transfer from gill to lung breathing during metamorphosis has been described, but the neural components underlying the two distinct respiratory rhythms, gill and lung, respectively, are not known. In addition, the cellular and network properties necessary to produce and coordinate gill and lung rhythms in the developing amphibian are poorly understood. The general goal of this collaborative research proposal is to characterize the mechanisms of metamorphic stasis due to prevention of lung inflation, an example of experience-dependent structural CNS plasticity.
In Specific Aims I, we will characterize the effects of the prevention of lung ventilation on the growth and respiratory behavior in intact tadpoles of Rana catesbeiana. It is our hypothesis that lung inflation is an essential part of respiratory metamorphosis, and we will test this hypothesis by assessing the effect of vagotomy or surgical denervation of the peripheral chemoreceptors or hypoxia alone on the progress of metamorphosis.
In Specific Aim II, we will test the hypothesis that prevention of lung inflation or ablation of afferent vagal information of lung inflation or ablation of peripheral chemoreceptor activity will delay the metamorphic development of lung ventilatory activity in an isolated brainstem preparation and suppress neural lung ventilatory responses to CO2 chemoreceptor stimulation.
In Specific Aim III, we will test the hypothesis that prevention of lung ventilation will delay or prevent the normal maturation of synaptic connections necessary to drive lung ventilation and delay the appearance of lung respiratory-related activity in individual motor neurons of cranial nerves V, VII, X and spinal nerve II. Amphibian models of respiratory control are attractive because they are relatively simple and provide insight into the ontogeny of the neural mechanisms necessary for gill and lung central pattern generation and central respiratory chemoreceptor function. Studies of amphibians have provided some of the first information about the ontogeny of respiratory control in vertebrates. Perturbations of the respiratory rhythm generating network may underlying the mechanisms of Sudden Infant Death Syndrome (SIDS), the apnea of prematurity, and sleep apnea in adults, and studies in amphibians may have wide neurobiological and medical relevance.
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