PROJECT SUMMARY: Overall Addiction is a chronic relapsing brain disorder resulting from perturbations in neural circuits. Delineating these circuit perturbations should provide a host of opportunities to develop new therapies for addiction prevention and treatment. New technologies in neuroscience are revolutionizing our ability to measure and intervene in specified neural circuits. To take advantage, these technologies should be broadly distributed. We propose to create a NIDA Center for Neural Circuits in Addiction at the University of Minnesota (UMN) to further develop and disseminate these new techniques to produce groundbreaking work in addiction neuroscience. Based on our collective expertise, our strong base of collaborative addiction research and the support provided by our institution, our group at the UMN is in an excellent position to form this Center. It would comprise four new Research Cores: 1) The Viral Innovation Core (VIC) will assist investigators in applying state-of-the-art viral manipulation approaches to their studies of the anatomical, molecular and neural circuit bases of addiction. This Core will provide expertise for design of custom vectors, including guidance on combinations of AAV serotype, promoters, and fluorescent tags; 2) The Structural Circuits Core (SCC) will offer state-of-the-art anatomical mapping of neural circuits involved in addiction. Integrated with the University Imaging Center and UMN Informatics Institute, SCC will provide automated use of brain clearing technology paired with meso- and micro- scale imaging of the CNS; 3) The Imaging Cells during Behavior Core (ICBC) will offer a range of imaging modalities to monitor brain activity in behaving animals across a range of spatial and temporal scales. These modalities include fiber photometry, head-mounted miniature microscopes (“miniscopes”) and novel wide field- of-view optical imaging during behavior at both the mesoscopic and cellular levels. 4) The Addiction Connectome Core (ACC) will create a computational platform to integrate multimodal functional and structural data to test relationships between exposure to addictive drugs and neural connectivity. Availability of this platform should enable outside scholars from anywhere in the world to delineate drug-modified connectivity patterns and addiction-relevant biological variables, facilitating the identification of biomarkers for mental function and dysfunction. Our Center would provide to the research community: a) Education and training in new technologies; b) Access to tools, reagents and expertise for data collection and analysis; c) Further development and adoption of new technologies; d) Catalysis of new collaborations among users; and e) Dissemination of resulting research and new technologies to the wider addiction research community. The Pilot Project Core will facilitate use of the Cores for innovative pilot studies and push the envelope in neural circuit research. Under the Center Director...