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The Role of Sensory Neurons Innervating Internal Organs

感觉神经元支配内脏器官的作用

基本信息

批准号：
10685444
负责人：
Ardem Patapoutian
金额：
$ 60.04万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-08-18 至 2027-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10685444
关键词：
3-Dimensional Ablation Address Adipocytes Adipose tissue Adrenergic Fibers Affect Afferent Neurons Anatomy Animal Experiments Autonomic nervous system Blood Pressure Brain Budgets Cells Central Nervous System Chemicals Cholera Toxin Protomer B Conscious Data Disparate Energy Metabolism Extravasation Fatty acid glycerol esters Female Fiber Future Gene Expression Genes Genetic Genetic Techniques Goals Hand Homeostasis Hormonal Human Image Interoception Intervention Investigation Ion Channel Knock-out Label Link Lipid Mobilization Lipids Literature Lung Maps Mediating Metabolic Methods Modeling Molecular Mus Muscle Nerve Neurons Nodose Ganglion Nutritional Obesity Operative Surgical Procedures Organ Output Pain Pattern Physiological Physiology Proteins Role Sensory Signal Transduction Skin Specificity Spinal Spinal Ganglia Stimulus Stretching Structure Sympathetic Nervous System Technology Temperature Testing Thermogenesis Tissues Touch sensation Tracer Unconscious State Vertebral column Viral Viral Vector Virus Visualization adeno-associated viral vector cost comparison experimental study genetic signature in vivo in vivo calcium imaging innovation insight intercellular communication invention loss of function male mechanical signal nerve supply novel novel strategies optogenetics programs response single-cell RNA sequencing somatosensory tool vector

项目摘要

Projection Summary Over the last decades, we have made tremendous advancements in understanding the role of somatosensory neurons in sensing exteroceptive signals including touch, temperature, and pain. However, somatosensory neurons also innervate internal organs, but we understand much less about the anatomy and physiology of these neurons. There is literature on the roles of interoceptive neurons in sensing lung stretch and blood pressure. These studies mainly focus on the Vagal Nodose ganglia that innervate many internal organs. However, dorsal root ganglia (DRG) neurons, in addition to innervating skin and muscle, also innervate disparate internal organs but have garnered much less focus. To begin to elucidate the structure and function of these sensory neurons, we focus on adipose-innervating DRG neurons. These neurons are an attractive starting point because very little is known about their form and function, but these neurons could potentially have a profound relationship with the autonomic nervous systems (for example, the sympathetic nervous system) and roles in whole-body physiology. Here, we show that fat depots are robustly innervated by DRG neurons. We have also collected important preliminary data molecularly defining the subset of DRGs that innervate fat depots, and have begun to address their interactions with the sympathetic activities. We propose to use state-of-the-art and innovative molecular and genetic techniques to map adipose-innervating DRG neurons, profile their identities, and test their function.

在过去的几十年里，我们在理解躯体感觉神经元在感知触觉、温度和疼痛等外感受信号中的作用方面取得了巨大的进步。然而，躯体感觉神经元也支配内脏器官，但我们对这些神经元的解剖学和生理学了解得少得多。有关于内感受神经元在感知肺伸展和血压中的作用的文献。这些研究主要集中在支配许多内脏器官的迷走结状神经节。然而，背根神经节（DRG）神经元除了神经支配皮肤和肌肉外，还神经支配不同的内脏，但受到的关注要少得多。为了开始阐明这些感觉神经元的结构和功能，我们集中在脂肪支配的DRG神经元。这些神经元是一个有吸引力的起点，因为对它们的形式和功能知之甚少，但这些神经元可能与自主神经系统（例如交感神经系统）和全身生理学中的作用有着深刻的关系。在这里，我们表明，脂肪库是由DRG神经元强大的神经支配。我们还收集了重要的初步数据，从分子上定义了支配脂肪库的DRG的子集，并开始讨论它们与交感神经活动的相互作用。我们建议使用最先进的和创新的分子和遗传技术来映射脂肪支配DRG神经元，配置文件的身份，并测试它们的功能。