Center for Neural Circuits in Addiction

项目总结：总体 上瘾是一种慢性复发性大脑疾病，由神经回路的扰动引起。勾勒出这些 电路干扰应该提供大量机会来开发新的成瘾预防和治疗方法 治疗。神经科学中的新技术正在彻底改变我们测量和干预特定疾病的能力 神经回路。为了利用这些技术，这些技术应该广泛分布。我们建议创建一个 明尼苏达大学(UMN)NIDA成瘾神经电路中心进一步开发和 传播这些新技术，以产生成瘾神经科学方面的开创性工作。基于我们的 集体专业知识，我们合作成瘾研究的强大基础，以及我们的 作为一个机构，我们在UMN的团队处于组建这个中心的绝佳位置。它将包括四个新的 研究核心：1)病毒创新核心(VIC)将协助研究人员应用最先进的病毒 他们研究成瘾的解剖学、分子和神经回路基础的操作方法。这 CORE将为定制媒介的设计提供专业知识，包括关于AAV血清型组合的指导， 启动子和荧光标签；2)结构电路核心(SCC)将提供最先进的解剖学 与成瘾有关的神经回路的映射。与大学影像中心和UMN整合 SCC信息学研究所将提供脑清理技术的自动使用，并与中、微观信息技术相结合 中枢神经系统的规模成像；3)行为期间成像细胞核心(ICBC)将提供一系列成像 在一系列空间和时间尺度上监测行为动物大脑活动的模式。这些 形式包括光纤光度学，头戴式微型显微镜(“迷你显微镜”)和新的广域-- 在介观和细胞水平上的行为期间的视场光学成像。4)上瘾 Connectome Core(ACC)将创建一个集成多通道功能和结构的计算平台 测试成瘾药物暴露和神经连接之间关系的数据。此平台的可用性 应该使来自世界各地的外部学者能够描绘出药物修饰的连接模式 与成瘾相关的生物变量，有助于识别心理功能和 功能障碍。我们的中心将为研究界提供：a)新技术方面的教育和培训； B)获得用于数据收集和分析的工具、试剂和专门知识；c)进一步开发和采用 新技术；d)促进用户之间的新协作；以及e)传播所产生的研究 并向更广泛的成瘾研究社区提供新技术。试验项目核心将促进使用 创新先导研究的核心，并推动神经电路研究的极限。在中心主任的 领导、行政核心和一个专家科学顾问小组将协调和支持 各个核心的努力。我们的目标是使该中心成为全国神经回路研究的资源 推动高影响力、协作性研究的技术，以解决我们领域的关键知识差距。

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’s leadership, the Administrative Core, with a panel of expert scientific advisors, would coordinate and support the efforts of the individual Cores. Our goal is for the Center to be a national resource for neural circuit research technologies that fuels high-impact, collaborative research to address critical knowledge gaps in our field.