Preclinical Core

临床前核心

• 批准号: 8740536
• 负责人: SHERYL S MOY
• 金额: $ 32.84万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8740536
• 关键词: Animals; Architecture; Atlases; Behavior; Behavioral; Biological Assay; Brain; Brain imaging; Caliber; Center for Translational Science Activities; Clinical; Consultations; Core Facility; Data; Development; Diffusion Magnetic Resonance Imaging; Embryo; Emotional; Engineering; Evaluation; Gene Expression; Genetic; Human; Image; Image Analysis; In Vitro; Interdisciplinary Study; Intervention Studies; Laboratories; Life; Magnetic Resonance; Magnetic Resonance Imaging; Measurement; Measures; Mental Retardation and Developmental Disabilities Research Centers; Methods; Microscopy; Microtus; Modeling; Molecular; Molecular Genetics; Morphology; Motor; Mus; Neonatal; Neurodevelopmental Disorder; Neuroglia; Neurons; Neurophysiology - biologic function; Phenotype; Preclinical Drug Evaluation; Process; Regimen; Research; Research Infrastructure; Research Personnel; Resources; Rodent; Scanning; Sensory; Services; Source; System; Techniques; Testing; Time; Tissues; Training; Work; base; brain cell; brain volume; cognitive function; computerized data processing; innovation; intellectual and developmental disability; interdisciplinary approach; migration; mouse model; multidisciplinary; mutant; neurodevelopment; neuroimaging; novel; optogenetics; pre-clinical; relating to nervous system; response; social; spatiotemporal; tool; translational neuroscience

Advances in the field of mouse genetics, including truly remarkable new strategies for controlled gene expression and engineering of mutant lines, have significantly enhanced the use of murine models in the study of intellectual and developmental disabilities (IDD). The Preclinical Core (PC) offers innovative, multidisciplinary approaches for measurement at the level of behavior, brain, and cell. These services are essential for IDDRC projects utilizing mouse models in genetic, molecular, neurobiologlcal, and preclinical intervention research. The Core has three components: the Mouse Behavioral Phenotyping Laboratory, the Confocal and Multiphoton Imaging Facility, and the Brain Imaging Analysis Service (for processing data from magnetic resonance (MRI) and diffusion tensor (DTI) imaging). By spanning multiple aspects of mouse model evaluation and use, these components provide a basis for integrative, translational neuroscience within the UNC IDDRC. The Core proposes four objectives to support high-caliber mouse model research: A.I. Provide innovative and translational behavioral phenotyping for genetic and environmental mouse models of neurodevelopmental disorders. The Mouse Behavioral Phenotyping Laboratory offers researchers a multifaceted test regimen, including assays for sensory, motor, social, emotional, and cognitive function, and approaches for neonatal behavior and preclinical drug screens. The PC also provides expertise, training, and access to a range of automated measurement systems for state-of-the-art phenotyping. A.2. Provide consultation, hands-on training, and cutting-edge resources for confocal, multiphoton, and widefield imaging. The Confocal and Multiphoton Imaging Facility offers a state-of-the-art microscopy laboratory, with multiple systems for evaluation of neural tissue in vitro and in living mice. Facility staff provide consultation and hands-on training in molecular and cellular microscopy techniques, including utilization of optogenetic and photosensitive probes, automated time-lapse imaging of neurons and glia, and multiphoton imaging of spatiotemporal dynamics in neuronal migration and connectivity in intact, living embryonic brains. A.3. Develop, utilize, and disseminate advanced methods for analysis of MRI and DTI scans from animal IDD models. The Brain Imaging Analysis Service devises innovative strategies for the processing and interpretation of brain imaging data, and methods to track abnormalities in neural development and function. The Service works to validate and optimize new methods to allow automated volumetric and connectivity analysis in MRIs of the developing rodent brain, and to validate measures applicable to both human and animal scans. Novel processing pipelines for segmentation and atlas-building, developmental brain atlases, and other critical tools for morphometric and functional analyses, are made publicly available. A.4. Facilitate integrative and multidisciplinary IDDRC research. The correlation of complementary mouse phenotypes, such as behavioral responses, dendritic morphology, cortical architecture, and regional brain volume and connectivity, provides a powerful approach to identify the mechanistic basis of abnormalities relevant to neurodevelopmental disorders. By combining behavior, microscopy, and neuroimaging, the PC offers IDDRC investigators the expertise, infrastructure, and collaborative opportunities for multidisciplinary research using mouse models. The PC is also a source of information on services provided by other UNC core facilities, and works to maintain strong connections with the Clinical Translational Core to enhance the relevance of mouse model work to studies in humans.

小鼠遗传学领域的进展，包括真正引人注目的受控基因新策略 突变系的表达和工程显着增强了小鼠模型在研究中的使用 智力和发育障碍（IDD）。临床前核心 (PC) 提供创新的、多学科的 行为、大脑和细胞层面的测量方法。这些服务必不可少 用于 IDDRC 项目，利用小鼠模型进行遗传、分子、神经生物学和临床前干预 研究。核心由三个部分组成：小鼠行为表型实验室、共聚焦实验室 和多光子成像设施，以及脑成像分析服务（用于处理来自 磁共振（MRI）和扩散张量（DTI）成像）。通过跨越小鼠模型的多个方面 评估和使用，这些组件为综合、转化神经科学提供了基础 北卡罗来纳大学国际DDRC。核心提出了四个目标来支持高水平的小鼠模型研究： 人工智能。为遗传和环境提供创新和转化行为表型 神经发育障碍小鼠模型。小鼠行为表型实验室提供 研究人员制定了多方面的测试方案，包括感觉、运动、社交、情感和认知分析 功能，以及新生儿行为和临床前药物筛选的方法。 PC还提供专业知识， 培训，并使用一系列用于最先进表型分析的自动测量系统。 A.2.提供共焦、多光子、 和宽场成像。共焦和多光子成像设施提供最先进的显微镜 实验室，具有用于评估体外和活体小鼠神经组织的多个系统。设施工作人员提供 分子和细胞显微镜技术的咨询和实践培训，包括利用 光遗传学和光敏探针、神经元和神经胶质细胞的自动延时成像以及多光子 完整的活胚胎大脑中神经元迁移和连接的时空动态成像。 A.3.开发、利用和传播用于分析 MRI 和 DTI 扫描的先进方法 动物 IDD 模型。脑成像分析服务设计了创新的处理和分析策略 脑成像数据的解释，以及跟踪神经发育和功能异常的方法。 该服务致力于验证和优化新方法，以实现自动体积测量和连接 对发育中的啮齿动物大脑进行 MRI 分析，并验证适用于人类和人类的措施 动物扫描。用于分割和图谱构建、发育大脑图谱的新颖处理流程， 以及用于形态测量和功能分析的其他关键工具已公开提供。 A.4.促进综合性和多学科的 IDDRC 研究。互补性的相关性 小鼠表型，例如行为反应、树突形态、皮质结构和区域 大脑体积和连接性，提供了一种强大的方法来识别异常的机制基础 与神经发育障碍有关。通过结合行为、显微镜和神经成像，PC 为 IDDRC 调查人员提供多学科的专业知识、基础设施和协作机会 使用小鼠模型进行研究。 PC 也是其他 UNC 提供的服务的信息来源 核心设施，并努力与临床转化核心保持紧密联系，以增强 小鼠模型工作与人类研究的相关性。