Neurobiology Core C

神经生物学核心 C

基本信息

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
项目类别：
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

项目摘要

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.

项目概要芝加哥肌肉骨骼疼痛中心 (C-COMP) 的总体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 斯隆疼痛机制的理解因此，为了促进新治疗靶点的确定，我们将利用现有的专业知识和创建神经生物学核心 C 的资源，该核心 C 将提供最先进的生理、转录和用于研究 MSK 疼痛机制的神经解剖学工具和科学专业知识。方法选择该核心中提供的内容是为了与核心 B 中提供的行为评估协同作用。研究周围和中枢神经系统机制的技术在过去的十年里，产生疼痛信号的协调变得更加复杂，导致对慢性疼痛状态背后的神经机制有许多新的见解。我们位于拉什和的实验室西北大学——在很大程度上是通过 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。这些复杂技术的采用然而，由于大多数实验室缺乏可用性，更广泛的 MSK 领域受到阻碍。资源和为此核心选择的服务是为了满足这一需求。我们自己综合积累的经验（超过 50 年）在连接神经科学和 MSK 斯隆方面建立了创新和国际领导地位领域，以及我们在这些不同技术方面的专业知识为我们提供了提供咨询服务的独特资格研究人员正在研究 MSK 斯隆疼痛的神经生物学。目标 1. 建立集中评估服务 MSK 疾病临床前模型周围神经系统的生理变化。这核心将为评估提供咨询、科学知识、技术培训和技术服务通过使用钙成像（包括体内钙成像）来研究感觉神经元生理学，电生理学和化学/光遗传学。目标 2. 建立转录组的集中资源周围神经系统分析。该核心将为以下人员提供培训和技术服务：收集并准备背根神经节 (DRG) 神经元用于 RNA-seq（批量和单细胞）。目标 3. 提供用于研究临床前 MSK 模型中神经解剖学可塑性的集中资源。核心将为进行周围神经系统的解剖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、RNAscope 原位杂交、DRG 细胞的组织培养以及标记特定类型细胞的遗传工具（记者小鼠、AAV）和光片成像。目标 4. 我们将举办研讨会并提供培训和强化项目，以增强 C-COMP 研究人员对如何进行实验的理解探索 MSK 斯隆和风湿性疾病的疼痛机制。