Investigating the Critical Role of Glia In Peripheral Organ Development and Physiology

项目摘要 人体的器官依赖于多个神经元回路的复杂整合来维持 动态平衡。例如，心脏必须对内部和外部刺激做出反应，并产生足够的血液 满足环境需求的流量。神经胶质细胞在支持神经系统功能方面起着关键作用，但也 对于建立适当的电路结构和生理来说是必不可少的。我们的实验室最近发现了一个细胞 在心脏上打字，与身体其他地方的星形胶质细胞群有许多相似之处。这种单元格类型， 我们称之为心脏神经节神经胶质细胞，它存在于心脏形成的过程中，对心脏的建立至关重要。 节奏。切除这些胶质细胞会导致心律失常和室颤，这两种情况都是严重的生理性的。 条件。本项目使用斑马鱼动物模型来研究斑马鱼的发育个体发育和 活体动物心脏发育过程中心脏神经节胶质细胞的形态特征(目标1)。另外， 探讨了这些胶质细胞和心肌细胞之间的功能关系及其在心脏调节中的作用 速度和节奏(目标2)。这些实验的结果将有助于我们理解 神经胶质细胞在周围神经系统中的多方面作用，并提供了关于 心脏神经节神经胶质细胞在心脏发育和疾病中的作用。 这项研究将在支持性和协作性的实验室环境中进行 圣母大学生物科学系。它将依靠该中心工作人员的专业知识 斑马鱼研究和综合成像设备。除了板凳技术的发展和 除了这个项目固有的技术专长，申请者还将磨练教学、指导和管理 这些技能将是她未来成功的关键，因为她是一名私人投资，在一家主要的 本科院校。

Project Summary Organs of the human body rely on complex integration of multiple neuronal circuits in order to maintain homeostasis. For example, the heart must respond to internal and external stimuli and produce sufficient blood flow to meet environmental demands. Glia play critical roles to support nervous system function but are also indispensable for establishment of appropriate circuit structure and physiology. Our lab recently identified a cell type in the heart with many similarities to astroglia populations found elsewhere in the body. This cell type, which we termed cardiac nexus glia, is present as the heart is being formed and is critical for establishment of heart rhythm. Ablation of these glia causes cardiac arrhythmia and ventricular fibrillation, both serious physiological conditions. This project uses the zebrafish animal model to investigate the developmental ontogeny and morphological characteristics of cardiac nexus glia in the developing hearts of living animals (Aim 1). Additionally, it probes the functional relationship between these glia and cardiomyocytes and their roles in modulating heart rate and rhythm (Aim 2). The results of these experiments will contribute crucial detail to our understanding of the multi-faceted roles of glia in the peripheral nervous system and provide important and specific insight about cardiac nexus glia function in heart development and disease. This research will be undertaken in a supportive and collaborative laboratory environment within the Biological Sciences Department at Notre Dame University. It will rely on expertise from staff of the Center for Zebrafish Research and the Integrated Imaging Facility. In addition to the development of bench skills and technical expertise inherent to this project, the applicant will also hone teaching, mentoring, and management skills that will be critical for her future success as a PI running her own research group at a primarily undergraduate institution.