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. [unreadable] [unreadable]