Stanford Neuroscience Research Cores for Gene Vectors, Microscopy, and Behavior

这项建议旨在建立必要的核心研究设施，以满足斯坦福神经科学研究界已确定的下列共同需求：(1)基因载体和病毒生产，(2)高级显微镜数据采集和分析，以及(3)自动行为表型分析。病毒载体用于表达重组蛋白和/或在脑组织中特定的细胞亚群中下调内源性蛋白的表达。甚至有可能表达能够在时间上精确控制单个神经元活动的蛋白质。这种病毒工具的使用正在给神经科学研究带来革命性的变化。一个集中的核心设施将极大地提高病毒生产的效率和成本效益。 三维图像分析和可视化对于量化来自体积成像技术的信息是必不可少的，例如阵列断层成像以及单光子和双光子共聚焦显微镜。这种类型的分析的软件和硬件都很昂贵，而且需要一个陡峭的学习曲线。这项提议将资助图像分析中心，这是一个拥有技术专长的中央资源，可以帮助科学家解决图像分析问题，并为现有的共享双光子组织切片设备建立电生理记录装置。 标准化的、可复制的行为测试对于将基础神经科学研究的进展转化为与人类疾病相关的治疗至关重要。自动化的行为表型分析可以通过消除因从家笼中取出而产生的压力和从测试环境中产生的新奇效应来提供更一致的结果。自动化测试还可以提高吞吐量和降低成本。这项提议将提供资金，以扩大现有核心设施中的自动行为测试能力。 这些核心设施将是SINTN努力的核心部分，以促进我们在分子、细胞和神经电路水平上对正常大脑和脊髓功能的了解，并阐明损伤或神经和精神疾病后神经系统功能障碍的潜在病理过程。 创建核心服务以满足这些共同的研究需求，将最大限度地减少不必要的设备重复，并为共同任务创造一个集中的专业知识来源，从而在更短的时间内获得更好的解决方案，从而提高效率和生产率。此外，由此产生的正式和非正式合作将为一个更丰富、更强大和更有活力的研究社区奠定基础。

This proposal seeks to establish essential core research facilities to meet the following identified shared needs of the Stanford Neuroscience research community: (1) gene vector and virus production, (2) advanced microscopy data acquisition and analysis, and (3) automated behavioral phenotyping. Viral vectors are used to express recombinant proteins and/or knock down expression of endogenous proteins in specific subsets of cells in brain tissue. It is even possible to express proteins that enable precise temporal control over the activity of individual neurons. Use of such viral tools is revolutionizing neuroscience research. A centralized core facility will vastly improve the efficiency and cost-effectiveness of virus production. Three dimensional image analysis and visualization are essential for quantifying information from volume imaging techniques, such as Array Tomography, and single- and two-photon confocal microscopy. Software and hardware for this type of analysis is expensive, and has a steep learning curve. This proposal will fund the Image Analysis Center, a central resource with technical expertise to assist scientists with image analysis problems, and an electrophysiological recording setup for an existing shared two-photon tissue slice rig. Standardized, replicable behavioral tests are critical to translating progress from basic neuroscience research to treatments relevant to human disease. Automated behavioral phenotyping can provide more consistent results by eliminating stress due to removal from the home cage and novelty effects from the test environment. Automated testing can also Improve throughput and reduce costs. This proposal will provide funds to expand capacity for automated behavioral testing in an existing core facility. These core facilities will be a central part of SINTN's effort to advance our understanding of normal brain and spinal cord function at the molecular, cellular, and neural circuit level, and to elucidate the pathological processes underlying malfunction of the nervous system following injury or neurologic and psychiatric diseases. Creating core services to meet these shared research needs will foster efficiency and productivity by minimizing the unnecessary duplication of equipment and creating a centralized source of expertise for shared tasks with the net effect of better solutions in less time. Moreover, the resulting formal and informal collaborations will provide the foundation for a richer, stronger, and more vibrant research community.