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

项目总结/摘要 及时准确地感知体内的信号对生存至关重要。通过迷走神经， 内感受系统和一个关键的身体-大脑轴，我们的大脑能够区分许多身体上多样化的 从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， 迷走神经感觉神经元（VSNs）的电生理特性已被广泛研究， 在过去的几十年里，它们的遗传异质性最近得到了很好的揭示。尽管有这些 尽管在理解个体迷走神经体脑回路的努力中，仍然不清楚这种重要的内感受性神经元是如何被激活的。 系统被组织成精确地呈现所有身体信号。的分子和功能结构， 感觉迷走神经仍然是一个谜。支配不同内脏的VSN是否有其独特的特征 器官？迷走神经如何编码不同的身体信号？在解剖学和分子学上 来感知来自不同内脏器官的相似/不同的输入？在这里，我们建议把知识和 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，以更好地了解这一关键的内感受系统的组织。此前我们 已经在迷走神经中开发了许多新的分子和遗传技术， 基于解剖结构和神经元活动的神经元身份的吞吐量分析。这里我们将 使用这些强大的工具来确定，通过三个特定的目标，迷走神经是否使用特定的 基因签名编码内脏器官，并形成模块化的解剖和功能单位，用于感知各种 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。 内感受系统我们相信，拟议的项目不仅将为划定 潜在的感觉机制，以及绘制不同的身体到大脑神经回路的遗传途径 和精确调节自主神经功能全面、系统地了解不同的身体- 大脑通路将在这一重要的内感受领域开辟新的前景，并可能带来新的概念， 治疗靶点进入神经保护领域。

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.