Center for Systems Neurogenetics of Addiction

项目总结总体构成部分 系统神经遗传学成瘾中心(CSNA)将行为研究的专业知识和努力结合在一起 神经学家、计算生物学家和遗传学家，他们各自将最先进的方法带到了 综合研究计划，将确定和模拟共同的潜在生物学机制 兴奋剂自我给药的生物行为风险。毒瘾是一种毁灭性的、高度复杂的 神经行为现象，以多种病因、分期和行为为特征 事实证明，很难结合起来研究。先进的小鼠遗传群体为评估 这些行为之间的关系，找到导致这些行为变异的遗传变异，并识别 它们相关的生物学机制和途径。我们将利用新的协作十字 遗传参考群体与多样性异交作图群体的生物学机制研究 通过易感特征预测自我服用精神刺激性药物可卡因的倾向。每个人 易感特征，包括冲动、急性和敏感的药物反应、追求奖励、青少年 尼古丁暴露和昼夜节律变化是该中心五个科学项目之一的研究内容。我们的方法 是史无前例的，因为我们将在表现出极端的老鼠种群中同时评估这些特征 遗传和表型变异，实现对共同和独特的全面和可扩展的评估 成瘾易感性的生物学机制。我们将明确和直接地确定特征的来源 在人口中的相关性。我们将生产功能基因组学和表型组学数据集，这将是 存放在广泛访问且功能强大的信息学资源中，可在此基础上进行扩展 由全球研究界提出。我们的中心还将产生新的、有效的小鼠突变体和复合体 成瘾相关现象的机制研究模型。除了帮助完成科学任务之外 我们的五个科学项目，我们的三个研究支持核心将提供经过验证的、最先进的和创新的 将技术扩展到更广泛的领域，包括：1)复杂、大容量的行为表型核心，2) 统计遗传学、分子图谱、生物库和数据的综合遗传学和基因组学核心 传播，以及3)鼠标资源和验证核心，用于交付新的鼠标资源 系统遗传学，体外和体内突变诱导和验证。行政核心将监督 有效协调、整合和传播中心的研究活动，并交付我们的 通过杰克逊实验室(JAX)的发现S建立了完善的教育项目。试点核心将 为更多的研究人员提供与该中心开展协作工作的机会。通过其组合 通过努力，CSNA将能够发现多种易感表型与 寻求和吸食毒品的倾向，为预防高危人群提供了新的机会 成瘾和对已经遭受痛苦的人的干预。

PROJECT SUMMARY OVERALL COMPONENT The Center for Systems Neurogenetics of Addiction (CSNA) synergizes the expertise and effort of behavioral neuroscientists, computational biologists and geneticists, who each bring state-of-the-art approaches to an integrated research program that will identify and model the common underlying biological mechanisms of biobehavioral risks for stimulant self-administration. Drug addiction is a devastating and highly complex neurobehavioral phenomenon, characterized by multiple etiological factors, stages and behaviors that have proven difficult to study in combination. Advanced mouse genetic populations provide a platform for evaluating the relationships among these behaviors, finding genetic variants responsible for their variation and identifying their associated biological mechanisms and pathways. We will make use of the new Collaborative Cross genetic reference population and Diversity Outbred mapping population to identify the biological mechanisms by which predisposing traits predict the tendency to self-administer the psychostimulant drug cocaine. Each predisposing trait, including impulsivity, acute and sensitized drug responses, reward-seeking, adolescent nicotine exposure and circadian variation, is studied in one of the Center's five scientific projects. Our approach is unprecedented in that we will evaluate these traits simultaneously in a mouse population exhibiting extreme genetic and phenotypic variation, enabling a holistic and extensible assessment of the common and distinct biological mechanisms of addiction vulnerability. We will definitively and directly identify sources of trait correlation in the population. We will produce functional genomics and phenomics datasets, which will be deposited in widely accessed and highly functional informatics resources, where they may be expanded upon by the global research community. Our Center will also generate novel, validated mouse mutants and complex models for mechanistic studies of addiction-related phenomena. In addition to aiding the scientific mission of our five scientific projects, our three research support cores will provide proven, state-of-the-art and innovative technologies to the broader field, including: 1) a sophisticated, large-capacity Behavioral Phenotyping Core, 2) an Integrative Genetics and Genomics Core for statistical genetics, molecular profiling, biobanking and data dissemination, and 3) a Mouse Resource and Validation Core for delivering novel mouse resources for systems genetics, in vitro and in vivo mutation induction and validation. The Administrative Core will oversee the effective coordination, integration and dissemination of the Center's research activities and deliver our findings through The Jackson Laboratory (JAX)'s well-established educational programs. The Pilot Core will offer additional investigators the opportunity to initiate collaborative work with the Center. Through its combined efforts, the CSNA will enable discovery of the mechanisms linking multiple susceptibility phenotypes to the propensity to seek and take drugs, opening up new opportunities for both prevention in those at risk for addiction and intervention in those already afflicted.