Rhythm control of lymnaea respiratory CPG neurons

呼吸的节律性活动是由被称为中枢模式发生器（central pattern generators， CPG）的特定神经细胞的神经网络控制的。CPG神经元之间突触连接的特异性对于产生和维持呼吸节律活动至关重要。然而，由于哺乳动物呼吸神经元网络的复杂性，呼吸CPG神经元的节律性活动是如何产生和调节的仍然未知。一种淡水池塘蜗牛，提供了一个简单的生物系统，在这个系统中，肺呼吸的节律活动是由三个CPG神经元控制的。我们最近建立了一个躯体-躯体突触模型，使我们能够在培养皿中研究呼吸节律活动。我们还建立了一个慢性缺氧蜗牛模型，该模型在整个动物中表现出呼吸活动的适应性促进。因此，蜗牛成为一个独特的模型来研究呼吸节奏是如何在多个层面上产生和调节的。我们拟以蜗牛为模型，研究特定基因/蛋白在调控CPG神经元特性中的作用。我们还将使用创新的实验方法，包括电生理学、分子生物学和光学成像技术，研究缺氧诱导的应激因子在呼吸网络节律调节中的作用。我们预计这些研究将为在单一系统中从分子水平到动物行为的呼吸活动的产生和控制提供新的见解。从这项研究中获得的信息将最终推进我们对呼吸生理学的理解，以及对呼吸系统疾病的潜在治疗。

Rhythmic activities of respiration are controlled by neuronal networks of the specific nerve cells named central pattern generators (CPG). Specificity of synaptic connections between the CPG neurons is critical for generating and maintaining respiratory rhythmic activities. However, how the rhythmic activity of respiratory CPG neurons is generated and regulated remains unknown, due largely to the complexity of mammalian respiratory neuronal networks. Lymnaea stagnalis, a fresh-water pond snail, offers a simple biological system in which the rhythmic activity of the lung breathing is controlled by three CPG neurons. We recently established a soma-soma synapse model which allows us to study the respiratory rhythmic activity in culture dish. We also developed a chronic hypoxia snail model which exhibits adaptive facilitation of respiratory activity in whole animal. Thus, the snail becomes a unique model to study how respiratory rhythm is generated and regulated at the multiple levels. Using the snail as a model, we propose to investigate the role of specific genes/proteins in regulating properties of the CPG neurons. We will also study the hypoxia-induced stress factors involved in rhythmic regulation of respiratory networks, using innovative experimental approaches including electrophysiological, molecular biological and optical imaging techniques. We anticipate that these studies will provide novel insights into the generation and control of respiratory activities from the molecular level to animal behavior in a single system. The information gained from this research will ultimately advance our understanding of not only respiratory physiology, but also potential treatment of respiratory disorders.