Behavioral modification of respiratory development

当早期发育阶段的蝌蚪被拒绝进入空气-水界面进行肺呼吸时，尽管有足够的温度，食物，氧气和光周期，变态也会被阻止。在变态过程中，从鳃呼吸到肺呼吸的发育转移已经被描述过，但是两种不同的呼吸节律，分别是鳃和肺，背后的神经成分是未知的。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尚不清楚。这项合作研究计划的总体目标是表征由于肺膨胀预防引起的变质停滞的机制，这是经验依赖的结构中枢神经系统可塑性的一个例子。在具体目的1中，我们将描述肺通气预防对完整的斑蛙蝌蚪生长和呼吸行为的影响。我们的假设是肺膨胀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周围化学感受器手术去神经支配或缺氧对变态进展的影响来验证这一假设。在Specific Aim II中，我们将验证以下假设：在孤立的脑干准备中，预防肺膨胀或消融肺膨胀的传入迷走神经信息或消融外周化学受体活性将延迟肺通气活动的变质发展，并抑制神经肺通气对CO2化学受体刺激的反应。在Specific Aim III中，我们将验证以下假设：肺通气的预防会延迟或阻止驱动肺通气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的单个运动神经元的肺呼吸相关活动的出现。两栖动物的呼吸控制模型是有吸引力的，因为它们相对简单，并提供了对鳃和肺中枢模式产生和中枢呼吸化学受体功能所需的神经机制的个体发生的见解。对两栖动物的研究提供了一些关于脊椎动物呼吸控制的个体发生的初步信息。呼吸节律产生网络的扰动可能是婴儿猝死综合征（SIDS）、早产儿呼吸暂停和成人睡眠呼吸暂停机制的基础，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.