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.

项目概要触摸对于我们的生存和社会联系至关重要，并且会因多种形式的伤害和伤害而受到干扰。尽管触摸转导具有根本重要性，但它仍然是人们最不了解的疾病状态之一。细胞和分子水平上的信号传递过程都是由嵌入在细胞中的受体介导的。皮肤，其中大部分由神经末梢和附属神经胶质或上皮细胞组成。对哺乳动物默克尔细胞复合体的研究表明，上皮细胞而不是神经元是然而，人们对神经胶质细胞对其他触觉功能的贡献知之甚少。感受器，包括帕西尼小体和迈斯纳小体，如果发现触觉感受器的神经胶质细胞能够感知和感知。介导机械力的传导，这一发现将构成范式转变，并可能表明我的实验室致力于将这些细胞作为治疗触觉障碍疾病的新靶点。过去 16 年，我们使用开创性的模型生物线虫来研究神经胶质细胞/神经元的交互作用。发现蠕虫鼻子触摸受体复合体的 Amphid 神经胶质细胞 (Amsh) 通过升高细胞内 Ca2+ 和 Cl- 这些结果表明 Amsh 神经胶质细胞可能具有检测机制。此外，我们发现 Amsh 胶质细胞中的 Ca2+ 反应暂时先于神经 Ca2+ 反应。反应，提出了神经胶质细胞可能是主要感觉细胞的有趣可能性。建议利用线虫遗传学、体内 Ca2+ 和 Cl- 成像工具以及简单的行为学剖析线虫鼻子中从基因到行为的神经胶质机械敏感性和神经胶质/神经元交互作用的分析我们相互关联但独立的目标是：1) 确定Ca2+瞬变的介导因素。触摸刺激下的阿姆什神经胶质细胞及其在触摸中的功能，2) 确定神经胶质细胞/神经元的机制触摸感受器中的串扰，以及 3) 确定是什么介导了触摸时 Amsh 胶质细胞 Cl- 的变化刺激及其在哺乳动物中的作用的开创性工作增进了我们对触觉的理解。然而，由于难以从皮肤获取触觉感受器，进展受到阻碍。以及哺乳动物系统的复杂性，我现在拥有前所未有的机会来利用这一点。之前的工作是使用遗传上更容易处理的模型来探索该领域的新领域 C. 我的工作可能会揭示与线虫相关的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。