Comprehensive Structural and Functional Mapping of the Mammalian Cardiac Nervous System

摘要 心血管疾病如心力衰竭、心律失常和高血压是发病的主要原因 和死亡率之间的关系。自主神经系统在神经系统中起着至关重要的作用。 这些疾病的病理生理学和神经轴调节提供了治疗的重要途径 干预我们研究团队的主要目标是精确定义心脏神经层次， 开发从宏观到细胞和分子水平的电路图，并在 与科学界保持联系。这项工作还将提供经过验证的方法和工具， 评估神经调节。研究小组将免费提供给科学界。一 跨物种的多尺度、多学科方法，与人类疾病高度相关，将用于 以高清晰度定义心脏神经支配的解剖结构。神经结构将与心脏功能联系起来。 心脏神经控制的复杂性需要一个综合的方法，这将是一个环法自行车赛 在该领域从“细胞到人”的最新解剖学、生理学和药理学方法 为了实现上述目标，必须结合起来。这一办法将在联合国系统各级采用。 神经轴（心脏、心外胸内神经结构和胸外神经结构）。的 提出的技术将允许，第一次，解剖和分子的详细描述， 在心脏和心外神经节的突触和细胞体水平的相互作用。使用的技术和 这些通路的整合代表了理解心脏神经控制的最创新尝试 曾经承诺过的。了解这些途径有可能加速治疗的发展， 将能够精确地瞄准神经结构，并指导方法重新利用已有的方法， 用于治疗目的的治疗（例如神经刺激器）。最终，这些方法需要 开发新型、有效和负担得起的干预措施，用于管理和预防心脏病， 心源性猝死

ABSTRACT Cardiovascular diseases such as heart failure, arrhythmias, and hypertension are leading causes of morbidity and mortality in the United States and world-wide. The autonomic nervous system plays a critical role in the pathophysiology of these diseases and neuraxial modulation provides an important avenue for therapeutic intervention. The major goal of our research team is to precisely define the cardiac neural hierarchy and develop circuit diagrams from the macroscopic to cellular and molecular levels and share these data on an ongoing basis with the scientific community. This effort will also provide verified methods and tools for assessing neuromodulation. The research team will make them freely available to the scientific community. A multiscale, multidisciplinary approach across various species, highly relevant to human disease, will be used to define the anatomy of cardiac innervation in high definition. Neural structure will be linked to cardiac function. The complexity of cardiac neural control necessitates an integrative approach that will represent a tour de force in this field. State-of-the-art anatomical, physiological, and pharmacological approaches from `cells to man' must be combined in order to achieve the above goals. This approach will be utilized at each level of the neuraxis (heart, extracardiac intrathoracic neural structures and extrathoracic neural structures). The techniques proposed will allow, for the first time, a detailed description of the anatomical and molecular interactions at the synaptic and cell body levels in cardiac and extracardiac ganglia. The techniques used and the integration of these pathways represents the most innovative attempt to understand cardiac neural control ever undertaken. Understanding these pathways has the potential to accelerate development of therapies that will be able to precisely target neural structures and also guide methods to re-purpose already available therapies (e.g. nerve stimulators) for therapeutic purposes. Ultimately, these approaches are required to develop novel, effective, and affordable interventions for the management and prevention of heart disease and sudden cardiac death.