Glia in Touch Sensation

神经胶质细胞在触觉中的作用

• 批准号: 8217077
• 负责人: Laura Bianchi
• 金额: $ 33.26万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-02-01 至 2016-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8217077
• 关键词: Affect; Afferent Neurons; Animals; Antigen-Presenting Cells; Area; Behavioral Assay; Biological Models; Caenorhabditis elegans; Caring; Cations; Cell physiology; Cells; Dyes; Electrophysiology (science); Epithelial Cells; Epithelium; Excretory function; Family; Fluorescence; Genetic; Goals; Hair; Human; Hyperalgesia; Image; Imaging Device; Individual; Inflammation; Injury; Ion Channel; Knock-out; Mammals; Measurement; Measures; Mechanics; Mediating; Merkel Cells; Modeling; Molecular; Molecular Genetics; Movement; Nerve; Nerve Endings; Nervous system structure; Neuroglia; Neurons; Output; Pacinian Corpuscles; Pain; Physiological; Play; Preparation; Process; Publishing; Receptor Activation; Regulation; Role; Ruffinis Corpuscles; Sensory; Skin; Stimulus; Stretching; System; Testing; Texture; Tissues; Touch sensation; Work; base; computerized data processing; epithelial Na+ channel; extracellular; feeding; knock-down; mechanical allodynia; member; nervous system disorder; neuronal excitability; novel; offspring; overexpression; patch clamp; public health relevance; research study; sensory neuropathy; social; tool

DESCRIPTION (provided by applicant): We depend on the sense of touch for most individual and social activities. Many forms of injuries and inflammation are accompanied by allodynia and mechanical hyperalgesia, conditions in which innocuous touch stimuli now cause severe pain. Despite its fundamental importance, mechanotransduction remains one of the least understood signaling process, both at the cellular and molecular levels. Touch is transduced by specialized mechanosensors embedded in the skin, most of which are composed of nerve endings and associated glial and epithelial cells. The role of these non-neuronal cells in touch sensation is poorly understood. Our goal is to understand touch sensation by dissecting functional interactions between mechanosensory neurons and glia using genetic, molecular and physiological strategies in C. elegans. Specifically, I hypothesize that such interactions employ the ion channel DELM-1, a member of the DEG/ENaC family of cationic channels, expressed in mechanosensory glia. Based on our preliminary results and what is known about the role of DEG/ENaC channels in epithelia, I hypothesize that glial DELM-1 is needed to control the concentration of K+ in the microenvironment between the neuronal ending and glia. Pilot experiments suggest that DELM-1 is inhibited by mechanical forces. Thus, I also hypothesize that the control of extracellular K+ by DELM-1 is highly dynamic and contributes to adaptation of the mechanosensors. The aims of this proposal are: 1) Does the glial DELM-1 channel regulate the activity of mechanosensory neurons? 2) Does DELM-1 elevate [K+] in the microenvironment between glia and touch neurons? 3) Is the glial DELM-1 channel mechanosensitive? Beautiful work in mammalian tissues using skin-nerve preparation and Von-Frey hair has allowed major progress in our understanding of touch sensation. I have now the unprecedented opportunity to capitalize on this previous work to explore a new area in the field. My work is likely to be relevant to our understanding of how associated cells, including glia, control the function of neurons throughout the nervous system. PUBLIC HEALTH RELEVANCE: Without the sense of touch we could not feed ourselves, hold objects, move around and care for our offspring. In many forms of injury and inflammation touch stimuli become painful. Touch is mediated by activation of receptors in the skin, most of which are composed of nerve cells and associated cells. The role of these associated cells in touch sensation is largely unknown. I propose here to advance our understanding of the functional interaction between nerve and associated cells in touch sensation using the tractable model system C. elegans. My work will ultimately help elucidate how cells associated with nerve cells contribute to sensory neuropathy and other human neurological disorders.

描述(由申请者提供)：我们依赖于大多数个人和社交活动的触觉。许多形式的损伤和炎症都伴随着痛觉过敏症和机械痛觉过敏，在这种情况下，无害的触摸刺激现在会导致严重的疼痛。尽管它的基本重要性，机械转导仍然是最不了解的信号过程之一，无论是在细胞和分子水平。触觉是由嵌入皮肤的专门机械传感器传递的，其中大部分由神经末梢和相关的神经胶质细胞和上皮细胞组成。人们对这些非神经细胞在触觉中的作用知之甚少。我们的目标是利用遗传、分子和生理策略，通过解剖机械感觉神经元和神经胶质细胞之间的功能相互作用来理解触觉。具体地说，我假设这种相互作用使用了离子通道Delm-1，它是DEG/ENaC阳离子通道家族的成员，表达在机械感觉胶质细胞中。根据我们的初步结果和关于DEG/ENaC通道在上皮细胞中所起作用的已知情况，我推测胶质细胞Delm-1是控制神经末梢和胶质细胞之间微环境中K+浓度所必需的。初步实验表明，Delm-1受到机械力的抑制。因此，我还假设Delm-1对细胞外K+的控制是高度动态的，并有助于机械传感器的适应。本研究的目的是：1)胶质细胞Delm-1通道是否调节机械感觉神经元的活动？2)Delm-1通道是否使胶质细胞和触觉神经元之间的微环境中的[K+]升高？3)胶质细胞Delm-1通道是否具有机械敏感性？在哺乳动物组织中使用皮肤神经准备和冯-弗雷头发的美丽工作使我们对触摸感觉的理解取得了重大进展。我现在有了前所未有的机会，可以利用这一先前的工作来探索该领域的一个新领域。我的工作可能与我们对相关细胞(包括胶质细胞)如何控制整个神经系统中神经元的功能的理解有关。 与公共健康相关：没有触觉，我们就无法养活自己、拿着物品、四处走动和照顾我们的后代。在许多形式的损伤和炎症中，触摸刺激会变得疼痛。触摸是通过激活皮肤上的感受器来调节的，其中大部分感受器由神经细胞和相关细胞组成。这些相关细胞在触觉中的作用在很大程度上是未知的。在这里，我建议使用易处理的模型系统线虫来促进我们对触摸感觉中神经和相关细胞之间的功能相互作用的理解。我的工作最终将有助于阐明与神经细胞相关的细胞如何导致感觉神经病和其他人类神经疾病。