Understanding the molecular and functional architecture of diverse body-brain pathways

了解不同体脑通路的分子和功能结构

• 批准号: 10503462
• 负责人: RUI CHANG
• 金额: $ 61.13万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10503462
• 关键词: Afferent Neurons; Anatomy; Architecture; Area; Brain; Code; Computational Biology; Development; Electrophysiology (science); Foundations; GTP-Binding Protein alpha Subunits, Gs; Genetic; Genetic Heterogeneity; Genetic Techniques; Health; Human; Individual; Interoception; Knowledge; Molecular; Molecular Genetics; Neurons; Neurosciences; Organ; Physiological; Physiology; Property; Research; Sensory; Signal Transduction; System; Time; Vagus nerve structure; Visceral; base; brain pathway; genetic approach; genetic signature; high throughput analysis; improved; innovative technologies; neural circuit; neurochemistry; neuroprotection; novel; response; sensory mechanism; therapeutic target; tool

Project Summary/Abstract Timely and precisely sensing signals inside the body is critical for survival. Through the vagus nerve, a major interoceptive system and a key body-brain axis, our brain is able to discriminate numerous physically diversified inputs from various visceral organs to generate appropriate physiological responses. Anatomical, neurochemical, and electrophysiological properties of vagal sensory neurons (VSNs) have been extensively investigated over the past several decades, and their genetic heterogeneity has been beautifully revealed recently. Despite these efforts in understanding individual vagal body-brain circuits, it is still unclear how this important interoceptive system is organized to precisely present all body signals. The molecular and functional architecture of the sensory vagus nerve remain to be a mystery. Are there unique features in VSNs innervating different visceral organs? How are different body signals coded by the vagus nerve? What are the anatomical and molecular basis for sensing similar/distinct inputs from different visceral organs? Here, we propose to bring knowledge and innovative technologies in neuroscience, physiology, genetics, and computational biology to this important interdisciplinary area to better understand the organization of this critical interoceptive system. Previously, we have developed a number of novel molecular and genetic techniques in the vagus nerve to enable high- throughput analysis of neuronal identities based on anatomical structures and neuronal activities. Here we will employ these powerful tools to determine, through three specific aims, whether the vagus nerve uses specific genetic signatures to code visceral organs and forms modular anatomical and functional units for sensing diverse body signals. We expect that studies proposed here will reveal many important details for this essential interoceptive system. We believe the proposed project will provide not only a critical foundation for delineating the underlying sensory mechanisms but also genetic access for charting distinct body-to-brain neural circuits and precise modulation of autonomic functions. A comprehensive and systematic understanding of diverse body- brain pathways will open up new vistas in this important area of interoception and may bring novel concepts and therapeutic targets into the field of neuroprotection.

项目摘要/摘要 及时，精确地感应体内的信号对于生存至关重要。通过迷走神经，一个专业 感受性系统和关键的身体脑轴，我们的大脑能够区分众多物理多样化 来自各种内脏器官的输入以产生适当的生理反应。解剖学，神经化学， 迷走神经元（VSN）的电生理特性已广泛研究 过去的几十年，他们的遗传异质性最近得到了精美的揭示。尽管如此 在理解单个迷走神经脑电路方面的努力，仍然不清楚这种重要的际观察如何 系统的组织以精确呈现所有身体信号。分子和功能性架构 感觉迷走神经仍然是一个谜。 VSN中是否有独特的特征来支配不同的内脏 器官？迷走神经编码不同的身体信号如何？解剖学和分子基础是什么 用于感知来自不同内脏器官的类似/不同的输入？在这里，我们建议带来知识和 神经科学，生理学，遗传学和计算生物学的创新技术 跨学科领域更好地了解这种关键的跨性别系统的组织。以前，我们 在迷走神经中开发了许多新型分子和遗传技术，以使高 基于解剖结构和神经元活性的神经元身份的吞吐量分析。我们会在这里 使用这些强大的工具通过三个特定目的确定迷走神经是否使用特定 编码内脏器官并形成模块化解剖和功能单位的遗传签名，以感知多样 身体信号。我们希望这里提出的研究将揭示这一重要的许多重要细节 感受性系统。我们认为，拟议的项目不仅将为划定的关键基础 潜在的感官机制，也是绘制不同人体到脑神经回路的遗传获取 和自主功能的精确调制。对各种身体的全面和系统的理解 - 大脑通道将在这一重要的互认为领域打开新的远景，并可能带来新颖的概念和 治疗靶标进入神经保护领域。