Preclinical Core

临床前核心

• 批准号: 9923809
• 负责人: SHERYL S MOY
• 金额: $ 33.94万
• 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 2020-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9923809
• 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; Diffusion Magnetic Resonance Imaging; Drug Screening; Embryo; Emotional; Engineering; Evaluation; Gene Expression; Genetic; Human; Image; Image Analysis; In Vitro; Infrastructure; Intellectual functioning disability; Interdisciplinary Study; Intervention Studies; Laboratories; Magnetic Resonance; Measurement; Measures; Mental Retardation and Developmental Disabilities Research Centers; Methods; Microscopy; Microtus; Modeling; Molecular; Morphology; Motor; Mus; Neonatal; Neurodevelopmental Disorder; Neuroglia; Neurons; Neurophysiology - biologic function; Phenotype; Photosensitivity; Regimen; Research; Research Personnel; Resources; Rodent; Scanning; Sensory; Services; Source; System; Techniques; Testing; Time; Tissues; Training; Work; behavioral response; brain cell; brain volume; cognitive function; computerized data processing; confocal imaging; imaging facilities; innovation; interdisciplinary approach; migration; mouse model; multidisciplinary; multiphoton imaging; mutant; neurodevelopment; neuroimaging; novel; optogenetics; pre-clinical; relating to nervous system; 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步，包括控制基因的真正杰出的新策略 突变线的表达和工程已经显着增强了研究中鼠模型的使用 智力和发育障碍（IDD）。临床前核（PC）提供创新的多学科 在行为，大脑和细胞水平上进行测量的方法。这些服务至关重要 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。核心具有三个组成部分：小鼠行为表型实验室，共焦 和多光子成像设施以及大脑成像分析服务（用于处理数据 磁共振（MRI）和扩散张量（DTI）成像）。通过跨越鼠标模型的多个方面 评估和使用，这些组件为综合，转化神经科学提供了基础 UNC IDDRC。核心提出了支持高素质小鼠模型研究的四个目标： 人工智能。为遗传和环境提供创新和转化的行为表型 神经发育障碍的小鼠模型。鼠标行为表型实验室提供 研究人员是一种多方面的测试方案，包括对感官，运动，社交，情感和认知的测定法 功能以及新生儿行为和临床前药物筛查的方法。 PC还提供专业知识， 培训，并访问用于最先进表型的一系列自动测量系统。 A.2。提供咨询，动手培训和尖端资源，用于共焦，多光顿， 和广场成像。共聚焦和多光子成像设施提供了最新的显微镜 实验室，具有多种系统，用于评估体外和活小鼠的神经组织。设施人员提供 分子和细胞显微镜技术的咨询和动手培训，包括利用 光遗传学和光敏探针，神经元和神经胶质的自动延时成像以及多光子 神经元迁移和完整的胚胎大脑中的连通性迁移和连通性中时空动力学的成像。 A.3。从 动物IDD模型。大脑成像分析服务为处理和 脑成像数据的解释以及跟踪神经发育和功能异常的方法。 该服务可以验证和优化新方法，以允许自动化和连接性 在MRI中分析发育中的啮齿动物大脑，并验证适用于人类和人的措施 动物扫描。用于分割和建造地图集的新型处理管道，发育大脑图书馆， 以及用于形态计量和功能分析的其他关键工具，可以公开使用。 A.4。促进综合和多学科IDDRC研究。互补的相关性 小鼠表型，例如行为反应，树突形态，皮质结构和区域性 大脑体积和连通性提供了一种强大的方法来识别异常的机械基础 与神经发育障碍有关。通过结合行为，显微镜和神经影像学，PC 为IDDRC调查人员提供多学科的专业知识，基础架构和协作机会 使用鼠标模型进行研究。 PC也是其他UNC提供的服务信息来源 核心设施，并致力于与临床翻译核心保持牢固的联系，以增强 小鼠模型与人类研究的相关性。