Glia in Touch Sensation

神经胶质细胞在触觉中的作用

基本信息

批准号：
8415886
负责人：
Laura Bianchi
金额：
$ 32.3万
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：
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/8415886
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

项目摘要

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.

描述（由申请人提供）：我们取决于大多数个人和社交活动的触觉。许多形式的伤害和炎症伴随着异常性痛和机械性痛觉过敏，无害的触摸刺激现在会导致严重的疼痛。尽管具有根本的重要性，但在细胞和分子水平上，机械转传仍然是最不理知识的信号传导过程之一。触摸是由嵌入皮肤中的专门机械传感器转导的，其中大多数由神经末端以及相关的神经胶质和上皮细胞组成。这些非神经元细胞在触摸感觉中的作用知之甚少。我们的目标是通过在秀丽隐杆线虫中使用遗传，分子和生理策略来解剖机械感觉神经元和神经胶质之间的功能相互作用，从而理解触摸感。具体而言，我假设这种相互作用采用了在机械感觉神经胶质中表达的阳离子通道的DEG/ENAC家族的离子通道Delm-1。根据我们的初步结果以及对DEG/ENAC通道在上皮中的作用的了解，我假设需要Glial Delm-1来控制K+在神经元结束和神经胶质之间的微环境中的K+浓度。试验实验表明，Delm-1受到机械力抑制。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。该提案的目的是：1）Glial Delm-1通道是否调节机械感知神经元的活性？ 2）Delm-1在神经胶质和触摸神经元之间的微环境中是否会提升[K+]？ 3）Glial Delm-1通道机械敏感吗？使用皮肤神经制剂和von-frey头发在哺乳动物组织中的精美作品使我们对触摸感的理解取得了重大进展。现在，我有一个前所未有的机会，可以利用这项以前的工作来探索该领域的新领域。我的工作可能与我们对关联细胞（包括神经胶质）如何控制神经元在整个神经系统中的功能的理解有关。