Preclinical Core

老鼠遗传学领域的进展，包括真正值得注意的控制基因的新策略 突变系的表达和工程，极大地加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 在行为、大脑和细胞层面进行测量的方法。这些服务是必不可少的 在遗传、分子、神经生物学和临床前干预中使用小鼠模型的IDDRC项目 研究。核心由三个部分组成：小鼠行为表型实验室、共焦 和多光子成像设备，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)。通过跨越鼠标模型的多个方面 评估和使用，这些组件为综合、翻译的神经科学提供了基础 北卡罗来纳大学国际数据中心。核心提出了四个目标来支持高水平的老鼠模型研究： A.I.为遗传和环境提供创新和翻译的行为表型 神经发育障碍的小鼠模型。小鼠行为表型实验室提供 研究人员提出了一种多方面的测试方案，包括感觉、运动、社交、情感和认知的测试 功能，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，以及使用一系列自动化测量系统进行最先进的表型鉴定。 A.2.提供有关共焦、多光子、 和宽视场成像。共焦和多光子成像设备提供最先进的显微镜 实验室，拥有多个系统，用于在体外和活着的小鼠中评估神经组织。设施工作人员提供 分子和细胞显微镜技术方面的咨询和实践培训，包括使用 光遗传和光敏探针、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、活的胚胎脑中神经元迁移和连接的时空动力学成像。 A.3.开发、利用和传播分析MRI和DTI扫描的高级方法 动物IDD模型。脑成像分析服务设计了处理和 解释大脑成像数据，以及追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，以实现自动体积和连接 分析发育中的啮齿类动物大脑的磁共振成像，并验证适用于人类和 动物扫描。用于分割和构建图谱的新型处理流水线，发育脑图谱， 以及用于形态测量和功能分析的其他关键工具都已公开提供。 A.4.促进综合和多学科的国际发展研究中心的研究。互补性的相关性 小鼠的表型，如行为反应、树突状细胞形态、皮质结构和区域 脑体积和连接性，为确定异常的机制基础提供了强有力的方法 与神经发育障碍有关。通过将行为、显微镜和神经成像相结合，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 使用老鼠模型进行研究。个人计算机也是关于其他UNC提供的服务的信息来源 核心设施，并致力于与临床翻译核心保持紧密联系，以增强 小鼠模型工作与人类研究的相关性。

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.