Preclinical Core

小鼠遗传学领域的进展，包括控制基因的真正显着的新策略 突变株的表达和工程改造，显著提高了研究中小鼠模型的使用 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 research.核心有三个组成部分：小鼠行为表型实验室，共聚焦 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，这些组件提供了一个基础，整合，翻译神经科学内 IDDRC.核心提出了四个目标来支持高水平的小鼠模型研究： A.I.为遗传和环境研究提供创新和转化的行为表型分析 神经发育障碍的小鼠模型。小鼠行为表型实验室提供 研究人员采用了多方面的测试方案，包括感官、运动、社交、情感和认知的测定。 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，并获得一系列自动化测量系统的国家的最先进的表型。 A.2.为共聚焦、多光子、 和宽视野成像。共焦和多光子成像设备提供了最先进的显微镜 实验室，具有用于在体外和活体小鼠中评估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，神经元和神经胶质的自动延时成像，以及多光子 在完整的，活的胚胎大脑中神经元迁移和连接的时空动力学成像。 A.3.开发、利用和传播先进的MRI和DTI扫描分析方法， IDD动物模型。脑成像分析服务设计了创新的处理策略， 大脑成像数据的解释，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，以实现自动化的体积和连接 在发育中的啮齿动物大脑的MRI分析，并验证适用于人类和 动物扫描用于分割和图谱构建的新处理管道，发育大脑图谱， 以及其他用于形态和功能分析的关键工具。 A.4.促进综合性和多学科的IDDRC研究。互补的相关性 小鼠表型，如行为反应、树突形态、皮质结构和区域 脑容量和连通性，提供了一个强有力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，基础设施和合作机会 使用小鼠模型的研究。个人电脑也是其他机构提供服务的信息来源。 核心设施，并致力于与临床翻译核心保持密切联系，以提高 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.