Center for Systems Neurogenetics of Addiction

项目概要 成瘾系统神经遗传学中心（CSNA）协同行为神经遗传学的专业知识和努力， 神经科学家，计算生物学家和遗传学家，他们每个人都带来了最先进的方法， 综合研究计划，将确定和模拟共同的潜在生物机制， 自我服用兴奋剂的生物行为风险。吸毒成瘾是一种毁灭性的高度复杂的 神经行为现象，其特点是多病因，阶段和行为， 很难结合起来研究。先进的小鼠遗传群体提供了一个平台， 这些行为之间的关系，寻找导致其变异的遗传变异， 相关的生物学机制和途径。我们将利用新的协作十字架 遗传参考群体和多样性远交作图群体，以确定生物学机制 通过这种方法，易患病的特质可以预测自我服用精神兴奋剂可卡因的倾向。每个 易患病特征，包括冲动、急性和致敏药物反应、奖赏寻求、青少年 尼古丁暴露和昼夜节律变化，是研究中心的五个科学项目之一。我们的方法 这是前所未有的，因为我们将在一个表现出极端 遗传和表型变异，从而能够对共同和独特的 成瘾脆弱性的生物学机制。我们将明确和直接地识别特征的来源 人口的相关性。我们将制作功能基因组学和表型组学数据集， 存放在广泛访问和高度功能的信息资源，在那里他们可能会扩大 全球研究界。我们的中心还将产生新的，经过验证的小鼠突变体和复杂的 成瘾相关现象的机制研究模型。除了帮助科学使命的 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 技术，以更广泛的领域，包括：1）一个复杂的，大容量的行为表型核心，2） 一个综合遗传学和基因组学核心，用于统计遗传学，分子分析，生物库和数据 传播，和3）小鼠资源和验证核心，用于提供新的小鼠资源， 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，并提供我们的 通过杰克逊实验室（JAX）完善的教育计划的研究结果。Pilot Core将 为其他研究者提供与中心开展合作的机会。通过其结合 通过这些努力，CSNA将能够发现将多种易感性表型与 寻求和服用药物的倾向，为预防那些有风险的人提供了新的机会， 成瘾和干预那些已经患病。

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.