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

项目摘要/摘要 及时而准确地感知体内的信号对生存至关重要。通过迷走神经，一个主要的 感官系统和一个关键的身体-脑轴，我们的大脑能够分辨出无数身体上的多样性 来自不同内脏器官的输入，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被完美地揭示了出来。尽管如此 在理解个体迷走神经-大脑回路的努力中，目前仍不清楚这种重要的内感 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。在支配不同内脏的VSN中有没有独特的特征 器官？迷走神经如何对不同的身体信号进行编码？什么是解剖学和分子基础？ 用于感知来自不同内脏器官的相似/不同的输入？在这里，我们建议将知识和 神经科学、生理学、遗传学和计算生物学的创新技术对这一重要 跨学科领域，以更好地理解这一关键的相互感觉系统的组织。此前，我们 已经在迷走神经中开发了许多新的分子和基因技术，以使高度... 基于解剖结构和神经元活动的神经元特性的吞吐量分析。在这里，我们将 使用这些强大的工具，通过三个特定的目标来确定迷走神经是否使用特定的 对内脏器官进行编码的遗传签名，并形成模块化的解剖学和功能单位，用于感知不同的 身体信号。我们预计，这里提出的研究将揭示这一关键问题的许多重要细节 联觉系统。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通路 以及对自主神经功能的精确调节。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领域开辟新的前景，并可能带来新的概念和 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.