Integrative Neuroscience Initiative on Alcoholism

描述(由申请人提供)： 长期接触酒精会导致神经适应现象，包括 耐受、敏感、依赖、戒断、饮酒失控， 以及导致过度饮酒的复发 消费。本申请书为“综合企业”联合体。 关于酒精中毒的神经科学倡议“(MA)(RFA：AA-01-002)是为了确定 分子、细胞和行为神经适应发生在 与延伸的杏仁核及其相关的脑奖赏回路 关系。据推测，遗传差异和/或 这一回路中的神经适应对个体负责 对过度饮酒的易感性存在差异。我们的 目标是：1)。建立动物模型以研究特定的神经生物学 易受伤害导致过度饮酒的目标 分子、细胞和神经电路层次的分析。2)。要确定 特定的基因簇，其表达受酒精调节，并且 对任何给定的过度饮酒模式负责，使用 基因表达阵列、差异显示、针对特定基因的突变 大脑区域，以及开发新的信息学工具来分析和 解释基因表达、细胞电路和大脑电路数据 通过使用转基因和基因敲除方法。3)。为了吸引新的和 通过招聘进入酒精研究领域的创新调查人员 个人获得发展性UOI赠款和试点项目，并通过发展 INIA科学家和其他人之间的在线互动能力，并通过使 神经信息学集成了可访问、可搜索和 与所有对酒精中毒感兴趣的科学家的其他数据库互动 研究。EIUA的结构被设想为三个亚组 跨三个领域的整合：依赖的动物模型和 神经适应亚群、神经回路亚群和分子基础 酗酒亚组。在每个领域都建立了核心设施 并包括遗传动物模型核心、基因表达核心和 分别为成像核心。每个小组由4-5个UOI提案组成 和1-3个发展性UOI研究建议。一个试点项目计划是 建议确定令人振奋的新研究领域，并继续 在酒精领域招募新的调查人员。INIA计划将 在行政核心的指导下，与集成的 神经信息学核心，通过指导委员会和持续的建议 科学咨询委员会的成员。

DESCRIPTION (provided by applicant): Chronic exposure to alcohol results in neuroadaptive phenomena, including tolerance, sensitization, dependence, withdrawal, loss of control of drinking, and relapse that contribute to the development of excessive alcohol consumption. This application for a Consortium for the "Integrative Neuroscience Initiative on Alcoholism" (MA) (RFA: AA-01-002) is to identify the molecular, cellular, and behavioral neuroadaptations that occur in the brain reward circuits associated with the extended amygdala and its connections. It is hypothesized that genetic differences and/or neuroadaptations in this circuitry are responsible for the individual differences in vulnerability to the excessive consumption of alcohol. Our goals are: 1). To establish animal models to study specific neurobiological targets for vulnerability that lead to excessive consumption of alcohol at the molecular, cellular and neural circuit levels of analysis. 2). To identify specific clusters of genes whose expression is regulated by alcohol and which are responsible for any given model of excessive alcohol consumption using gene expression arrays, differential display, mutagenesis directed at specific brain areas, and the development of new informatics tools to analyze and interpret gene expression, cellular circuitry and brain circuitry data and with the use of transgenic and knockout approaches. 3). To attract new and innovative investigators to the field of alcohol research by recruiting individuals for developmental UOI grants and pilot projects and by developing online interactive capacity among INIA scientists and others, and by making the neuroinformatics integrated data sets accessible, searchable and interactive with other databases for all scientists interested in alcoholism research. The structure of EIUA is envisioned as three subgroups that integrate across three domains: Animal Models of Dependence and Neuroadaptation Subgroup, Neurocircuitry Subgroup, and Molecular Basis of Excessive Drinking Subgroup. Core facilities are established in each domain and include the Genetic Animal Models Core, the Gene Expression Core and the Imaging Core, respectively. Each Subgroup is comprised of 4-5 UOI proposals and 1-3 Developmental UOI research proposals. A Pilot Project program is proposed to identify exciting new areas for research and the continual recruitment of new investigators to the alcohol field. The INIA program will be directed by an Administrative Core in close cooperation with the Integrated Neuroinforinatics Core via a Steering Committee and with the continual advice of the Scientific Advisory Committee.