Behavioral modification of respiratory development

当发育早期的蝌蚪被拒绝进入空气-水界面呼吸时，即使有足够的温度、食物、氧气和光周期，变态也会停止。已经描述了变态过程中从鳃到肺呼吸的发育转移，但分别支持鳃和肺这两种不同呼吸节律的神经成分尚不清楚。此外，在发育中的两栖动物中，产生和协调鳃和肺节律所必需的细胞和网络特性还知之甚少。这项合作研究提案的总体目标是表征由于防止肺膨胀而导致的变性瘀滞的机制，这是经验依赖的结构中枢神经系统可塑性的一个例子。在特定的目标I中，我们将表征阻止肺通风对完整的儿蛙蝌蚪生长和呼吸行为的影响。我们的假设是肺充气是呼吸变态的重要组成部分，我们将通过评估迷走神经切断术或外科手术去神经周围化学感受器或单纯缺氧对变态过程的影响来检验这一假说。在特定的目标II中，我们将检验这样一种假设，即防止肺膨胀或消融肺充气的传入迷走神经信息或消融外周化学感受器活动将延缓隔离脑干制备的肺通风活动的变性发展，并抑制对CO2化学感受器刺激的神经性肺通气反应。在特定的目标III中，我们将验证这样的假设：阻止肺通风将延迟或阻止驱动肺通风所需的突触连接的正常成熟，并延迟脑神经V、VII、X和脊神经II的单个运动神经元中与肺呼吸相关的活动的出现。呼吸控制的两栖动物模型之所以吸引人，是因为它们相对简单，并提供了对鳃和肺中枢模式生成和中枢呼吸化学感受器功能所需的神经机制的个体发育的洞察。对两栖动物的研究为脊椎动物呼吸控制的个体发育提供了一些最早的信息。呼吸节律生成网络的紊乱可能是婴儿猝死综合征(SID)、早产儿呼吸暂停和成人睡眠呼吸暂停的潜在机制，对两栖动物的研究可能具有广泛的神经生物学和医学意义。

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.