Neurobiology Core C

神经生物学核心 C

• 批准号: 10488613
• 负责人: RICHARD J MILLER
• 金额: $ 27.24万
• 依托单位: RUSH UNIVERSITY MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-14 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10488613
• 关键词: Adoption; Afferent Neurons; Anatomy; Animals; Area; Behavior assessment; Brain; Brain imaging; Calcium; Cells; Chicago; Collaborations; Communities; Consult; Consultations; Core Facility; Custom; Data Analyses; Development; Electrophysiology (science); Evaluation; Fostering; Functional Magnetic Resonance Imaging; Funding; Future; Genetic; Genetic Transcription; Goals; Human; Image; Immunohistochemistry; In Situ Hybridization; International; Joints; Knee; Label; Laboratories; Leadership; Learning; Methods; Microscopy; Modeling; Monitor; Mus; Musculoskeletal; Musculoskeletal Diseases; Musculoskeletal Pain; National Institute of Arthritis and Musculoskeletal and Skin Diseases; Needs Assessment; Neuraxis; Neuroanatomy; Neurobiology; Neurons; Neurosciences; Pain; Pain Research; Pathway interactions; Peripheral; Peripheral Nervous System; Physiological; Physiology; Positron-Emission Tomography; Pre-Clinical Model; Publications; Reporter; Research; Research Personnel; Research Support; Research Training; Resources; Rheumatism; Running; Services; Spinal Ganglia; Surveys; Technical Expertise; Techniques; Technology; Training; Translations; Universities; Work; base; cell type; chronic pain; experience; ganglion cell; in vivo calcium imaging; innovation; insight; nerve supply; neuromechanism; new technology; new therapeutic target; optogenetics; pain signal; pre-clinical; prevent; programs; single-cell RNA sequencing; tissue culture; tool; transcriptome sequencing; validation studies; web portal

Project summary The overarching goal of the Chicago Center on Musculoskeletal Pain (C-COMP) is to foster and support research and training aimed at understanding the mechanisms underlying pain associated with musculoskeletal (MSK) diseases, with the ultimate goal of better managing and preventing it. To support high- quality, innovative research that will accelerate our understanding of the mechanisms underlying MSK pain and, hence, facilitate identification of new therapeutic targets, we will capitalize on existing expertise and resources to create a Neurobiology Core C that will provide state-of-the-art physiological, transcriptomal, and neuroanatomical tools as well as scientific expertise for studying the mechanisms of MSK pain. The methods offered in this core have been chosen to synergize with the behavioral assessments offered in Core B. Technologies for studying the mechanisms through which the peripheral and central nervous systems coordinate to produce pain signaling have become much more sophisticated over the last decade, leading to many new insights into the neural mechanisms underlying chronic pain states. Our laboratories at Rush and Northwestern University - in large parts through NIAMS supported funding - have led the way in developing these tools for use in studying MSK pain in particular. The adoption of these sophisticated techniques in the broader MSK field is, however, hindered by a lack of availability to most laboratories. The resources and services selected for this core have been chosen to fill this need. Our own combined cumulative experience (>50 years) and established innovation and international leadership in bridging the neuroscience and MSK fields, and our expertise in these various technologies provides us with unique qualifications for advising researchers studying the neurobiology of MSK pain. Aim 1. Establish a centralized service for assessing physiological changes in the peripheral nervous system of preclinical models of MSK disease. The Core will provide consultation, scientific expertise, technical training, and technical services for the evaluation of sensory neuron physiology through the use of calcium imaging, including in vivo calcium imaging, electrophysiology, and chemo/opto-genetics. Aim 2. Establish a centralized resource for transcriptomal analysis of the peripheral nervous system. The Core will provide training and technical services for collecting and preparing dorsal root ganglia (DRG) neurons for RNA-seq (bulk and single cell). Aim 3. Provide a centralized resource for studying plasticity in neuroanatomy in preclinical MSK models. The core will provide technical assistance and training for performing anatomical studies of the peripheral nervous system - particularly joint innervation, including intra-articular innervation, immunohistochemistry of DRG, RNAscope in situ hybridization, tissue culture of DRG cells, and genetic tools for labeling particular types of cells (reporter mice, AAVs), and lightsheet imaging. Aim 4. We will present seminars and provide training and enrichment programs for enhancing the understanding of C-COMP investigators in how to experimentally explore mechanisms of pain in MSK and rheumatic diseases.

项目摘要 芝加哥肌肉骨骼疼痛中心（C-COMP）的首要目标是促进和支持 研究和培训，旨在了解与疼痛相关的潜在机制， 肌肉骨骼（MSK）疾病，最终目标是更好地管理和预防它。为了支持高- 高质量的创新研究，将加速我们对MSK疼痛机制的理解 因此，促进新的治疗靶点的识别，我们将利用现有的专业知识， 资源，以创建一个神经生物学核心C，将提供最先进的生理，转录， 神经解剖学工具以及研究MSK疼痛机制的科学专业知识。的方法 选择本核心中提供的行为评估与核心B中提供的行为评估协同作用。 研究外周和中枢神经系统 在过去的十年里，协调产生疼痛信号的机制变得更加复杂， 对慢性疼痛状态下的神经机制有许多新的见解。我们在拉什的实验室， 西北大学-在很大程度上通过NIAMS支持的资金-在开发方面处于领先地位 这些工具特别适用于研究MSK疼痛。这些先进的技术在 然而，由于大多数实验室缺乏可用性，更广泛的MSK领域受到阻碍。的资源和 为这一核心选定的服务就是为了满足这一需要。我们积累的经验 （>50年），并在神经科学和MSK之间建立了创新和国际领导地位 我们在这些不同技术领域的专业知识为我们提供了独特的咨询资格 研究MSK疼痛的神经生物学的研究人员。目标1。建立集中评估服务 MSK疾病的临床前模型的外周神经系统的生理变化。的 核心将为评估提供咨询、科学专门知识、技术培训和技术服务 通过使用钙成像，包括体内钙成像， 电生理学和化学/光遗传学。目标2.为转录组建立集中资源 分析周围神经系统。核心小组将为下列人员提供培训和技术服务： 收集和制备背根神经节（DRG）神经元用于RNA-seq（整体和单细胞）。目标3。提供 一个集中的资源研究可塑性神经解剖学在临床前MSK模型。芯会 为进行周围神经系统解剖学研究提供技术援助和培训- 特别是关节神经支配，包括关节内神经支配，DRG的免疫组织化学， DRG细胞的原位杂交、组织培养和用于标记特定类型细胞的遗传工具（报告基因 小鼠，AAV）和光片成像。目标4。我们将举办研讨会，提供培训， 丰富的程序，以提高C-COMP研究人员在如何实验的理解， 探索肌肉萎缩症和风湿性疾病的疼痛机制。