权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Glial ion channels in glia/neurons interactions

神经胶质/神经元相互作用中的神经胶质离子通道

基本信息

批准号：
10749239
负责人：
Laura Bianchi
金额：
$ 38.38万
依托单位：
UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-06-01 至 2028-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10749239
关键词：
Adenylate Cyclase Antigen-Presenting Cells Area Basic Science Behavior Behavioral Assay Brain Caenorhabditis elegans Calcium Caring Cells Communication Complex Cyclic AMP Data Dedications Disease Endowment Environment Epithelial Cells Exclusion Feedback Functional Imaging Funding Genes Genetic Goals Harvest Human Image Imaging Device Injury Ion Channel Knock-out Mammals Mediating Meissners Corpuscle Merkel Cells Modeling Molecular Nerve Nerve Endings Nervous System Neuroglia Neuromodulator Neurons Neuropeptides Neurotransmitters Nose Organ Organism Output Perception Physiology Play Process Publishing Regulation Role Sensory Serotonin Signal Transduction Skin System Testing Touch sensation Transducers Trauma Vertebrates Work cell type epithelial Na+ channel excitatory neuron experimental study gamma-Aminobutyric Acid glial activation in vivo knock-down mechanical force model organism mutant neuronal excitability neurotransmission novel offspring optogenetics receptor repaired response sensory system serotonin receptor social attachment tool transcriptome sequencing

项目摘要

PROJECT SUMMARY Touch is essential for our survival and for social bonding, and in disrupted in many forms of injuries and disease states. Despite its fundamental importance, touch transduction remains one of the least understood signaling processes, both at the cellular and molecular levels. Touch is mediated by receptors imbedded in the skin, most of which are composed of nerve endings and accessory glial or epithelial cells. Groundbreaking work on the mammalian Merkel cells complex demonstrated that the epithelial cell, rather than the neuron, is the primary sensory cell. However, little is known about the contribution of glia to the function of other touch receptors, including the Pacinian and Meissner’s corpuscles. If glia of touch receptors are found to sense and mediate the transduction of mechanical forces, this finding would constitute a paradigm shift and may suggest these cells as novel targets for the treatment of conditions in which touch is disrupted. My lab has dedicated the last 16 years to the study of glia/neuron cross talk using the pioneering model organism C. elegans. We found that Amphid glial cells (Amsh) of the worm nose touch receptor complex respond to touch by rise of intracellular Ca2+ and Cl-. These results suggest that Amsh glia may be endowed with mechanisms that detect mechanical forces. Furthermore, we found that Ca2+ responses in Amsh glia temporally precede neuronal Ca2+ responses, raising the intriguing possibility that glia might be the primary sensory cells. The goal of this proposal is to leverage C. elegans genetics, in vivo Ca2+ and Cl- imaging tools, and straightforward behavioral assays to dissect from gene to behavior glial mechanosensitivity and glia/neuron cross talk in the worm nose touch receptor. Our inter-related but independent aims are: 1) To determine what mediates Ca2+ transients in Amsh glia upon touch stimulation and their function in touch, 2) To identify mechanisms of glia/neuron crosstalk in touch receptors, and 3) To determine what mediates Amsh glial Cl- changes upon touch stimulation and their function in touch. Pioneering work in mammals has advanced our understanding of touch sensation. However, progress has been hindered by the difficulty of harvesting touch receptors from the skin and the complexity of the mammalian system. I have now the unprecedented opportunity to capitalize on this previous work to explore a new area in the field using the genetically amenable and more tractable model C. elegans. My work is likely to reveal general principles of glial function and glia/neuron crosstalk relevant to other sensory systems and other parts of the nervous system.

项目摘要触摸对于我们的生存和社会联系是必不可少的，在许多形式的伤害和破坏中，疾病状态。尽管它的基本重要性，触摸传导仍然是最不了解的信号过程，无论是在细胞和分子水平。触摸是由嵌入在大脑皮层中的感受器介导的。皮肤，其中大部分由神经末梢和辅助神经胶质细胞或上皮细胞组成。开创性对哺乳动物默克尔细胞复合体的研究表明，初级感觉细胞然而，关于胶质细胞对其他触觉功能的贡献，受体，包括Pacinian和Meissner小体。如果发现触觉感受器的神经胶质能够感知和介导机械力的转导，这一发现将构成一个范式转变，并可能表明这些细胞作为治疗触摸中断的病症的新靶点。我的实验室致力于在过去的16年里，使用先驱模式生物C.优雅的我们发现蠕虫鼻触觉受体复合体的Amphid神经胶质细胞（Amsh）通过增加细胞内Ca ~（2+）和Cl ~-。这些结果表明，AMSH神经胶质细胞可能被赋予了检测机制，机械力此外，我们还发现，在神经元Ca ~（2+）反应之前，AMSH神经胶质细胞的Ca ~（2+）反应时间神经胶质细胞可能是初级感觉细胞。这个目标建议是利用C. elegans遗传学，体内Ca 2+和Cl-成像工具，以及直接的行为分析从基因到行为的神经胶质机械敏感性和蠕虫鼻中的神经胶质/神经元串扰触觉感受器我们相互关联但独立的目标是：1）确定是什么介导了Ca 2+瞬变，触觉刺激下的Amsh胶质细胞及其在触觉中的功能; 2）探讨胶质细胞/神经元在触觉刺激下的作用机制触觉感受器中的串扰，以及3）为了确定在触摸时介导Amsh神经胶质Cl-变化的因素刺激及其在触摸中功能。哺乳动物的开创性工作推进了我们对触觉的理解感觉。然而，从皮肤中获取触觉感受器的困难阻碍了进展和哺乳动物系统的复杂性。我现在有一个前所未有的机会来利用这一点以前的工作，探索一个新的领域，在该领域使用遗传上的顺从和更容易处理的模型C。优雅的我的工作很可能揭示神经胶质功能和神经胶质/神经元串扰的一般原理，其他感觉系统和神经系统的其他部分。