Core Facilities for Analysis of Neural Circuit Structure and Function

这项拨款提案的目的是建立一套核心设施，将新技术的理解和使用传播给我们社区的广大神经科学家。我们要求为三个相互关联的科学核心设施和一个行政核心设施提供资金。科学核心如下：(1)先进的成像技术，使神经科学家能够利用最新的光学成像技术和高通量电子显微镜，以高特异性和高分辨率可视化神经回路的结构和功能；(2)神经工程，将提供设计和制造专业知识，使个人用户能够适应最新的电子、成像和计算机技术用于他们的实验；(3)基因组修饰，这将产生并提供转基因和靶向突变小鼠，特别是那些神经元群体被标记用于结构或功能分析的小鼠。一个额外的设施，专门用于神经成像，由其他来源支持，将与这里支持的设施整合，为神经科学家提供全面的成像模式，目前推动该领域向前发展。最后，一个行政核心将跟踪所有科学核心的使用和财务状况，并监督与神经成像的协调，以及促进核心用户和核心技术人员之间的互动。个人将在这些核心中找到设备和服务，而这些设备和服务很难或不可能在缺乏足够技术专长、资金和空间的单个实验室中得到支持。这组用户主要来自跨学科和跨部门的脑科学中心，通过共享空间、设备和技术以及用户会议，将被吸引到一个更紧密的社区。我们也明白，许多这些新技术很难理解和实现，因此它们没有像希望的那样得到广泛的利用。因此，我们建议不仅要建立这些核心，而且要采取多种战略，以减少对其广泛利用的障碍。这些措施包括正规和非正规教育，免费提供大多数核心服务，并提供充分的技术支持。通过实施这一雄心勃勃的模型，我们希望将神经科学研究的范式从完全依赖以实验室为中心的个体设施转变为更经济有效地使用非凡的共享设施。因此，这些核心不仅有助于产生有价值的研究成果，而且还将促进跨学科神经科学的新模式。

The aim of this grant proposal is to establish a set of core facilities that will spread understanding and use of new technologies to the wide range of neuroscientists in our community. We are requesting funding for three interrelated scientific core facilities plus an administrative core. The scientific cores are as follows: (1) Advanced imaging, which will enable neuroscientists to visualize neural circuit structure and function with great specificity and resolution using both the newest optical imaging technology and high-throughput electron microscopy; (2) Neuro-engineering, which will provide design and fabrication expertise to allow individual users to adapt the latest electronic, imaging, and computer technologies for their experiments; and (3) Genome modification, which will generate and provide transgenic and targeted mutant mice, especially those in which neuronal populations are marked for structural or functional analysis. An additional facility, devoted to Neuroimaging, supported from other sources, will be integrated with those supported here, providing neuroscientists with access to the full range of imaging modalities currently driving the field forward. Finally, an Administrative core will track the usage and finances of all of the scientific cores and oversee coordination with neuroimaging, as well as facilitating interactions between the core users and core technical staff. Individuals will find equipment and services in these cores that are difficult or impossible to support in individual labs, which lack sufficient technical expertise, money, and space. The group of users, primarily drawn from the interdisciplinary and interdepartmental Center for Brain Science, will be drawn into a closer community, through shared space, equipment, and techniques, as well as user meetings. We also understand that many of these newer technologies are difficult to understand and implement, and so they are not utilized as broadly as might be wished. Thus we propose not only to establish these cores but also to adopt multiple strategies aimed at reducing barriers to their widespread utilization. These include formal and informal education, making most core services available without user fees, and providing ample technical support. By implementing this ambitious model we hope to shift the paradigm for neuroscience research from complete reliance on individual laboratory-centered facilities to the more cost-effective and productive use of extraordinary shared facilities. The cores will thereby not only contribute to generation of valuable research results but also promote a new model for interdisciplinary neuroscience.