Neurocircuitry Mapping and Genotyping Core

神经回路图谱和基因分型核心

• 批准号: 7214345
• 负责人: ROBERT J. HITZEMANN
• 金额: $ 23.77万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-27 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7214345
• 关键词: 6 hydroxydopamine; alcoholic beverage consumption; amygdala; autoradiography; behavioral /social science research tag; brain regulatory center; cooperative study; dopamine receptor; dopamine transporter; ethanol; experimental brain lesion; gene expression; gene targeting; genetically modified animals; immunocytochemistry; in situ hybridization; laboratory mouse; preference; receptor expression; substance abuse related behavior; western blottings

DESCRIPTION (provided by applicant): Three behavioral models of excessive ethanol consumption (DID, SHAC and WID) are widely used throughout the INIA-West consortium. A fourth model intragastric consumption (IGC) is used at only one site but importantly provides a novel mouse model of what is likely to be dependence-induced drinking. A primary purpose of this core is to provide a standardized assessment of the circuits that are associated with each of these models and the changes in these circuits as the models are modified by genetic and/or pharmacologic procedures. The following aims have arranged the planned activities of the core in a systematic fashion, moving from the basic models to variations on the models. The advantage from a mapping perspective of the DID, SHAC and WID procedures is that the ethanol is consumed in a limited access period which allows one to access the circuits associated with both the initiation and continuation of the drinking episode. The proposed core has four aims/goals: 1. To map in C57BL/6J (B6) mice the circuits associated with DID, SHAC, WID and IGC using as appropriate a combination of in situ hybridization(ISH) and immunohistochemical (IHC) techniques. These studies will examine whether or not there are distinct circuits associated with the initiation and maintenance of a drinking episode. Given the widespread use of B6 mice throughout INIA-West, these data will serve as the primary reference circuits. 2. To map the relevant circuits in new genetic animal models. For DID and SHAC, replicate selected lines will be bred from heterogenous stock (HS/Npt) animals (Crabbe and Finn). The data obtained will be contrasted with the results obtained in specific aim 1. 3. To utilize the genetic and pharmacological variations on the four models to further refine the circuits associated with excessive ethanol consumption. Several UO1 applications plan to investigate variations on the basic behavioral models in order to refine at the anatomical and/or molecular level the relevant circuits. These data can be contrasted with the results obtained in aims 1 and 2. Importantly, aims 1-3 must be viewed as part of an iterative process. The core will begin to identify the relevant circuits, investigators will test the most promising targets which in turn will generate new models and thus, additional core activity. The core will also provide (aim 4) tissue for gene array and proteomics analyses and a high thoughput SNP genotyping facility for all INIA-West investigators.

描述（由申请人提供）：INIA-West 联盟广泛使用三种过量乙醇消耗行为模型（DID、SHAC 和 WID）。第四种模型胃内消耗（IGC）仅在一个部位使用，但重要的是提供了一种可能是依赖引起的饮酒的新型小鼠模型。该核心的主要目的是提供对与每个模型相关的回路以及当模型通过遗传和/或药理学程序修改时这些回路的变化的标准化评估。以下目标以系统的方式安排了核心计划的活动，从基本模型转向模型的变化。从 DID、SHAC 和 WID 程序的映射角度来看，其优点是乙醇在有限的访问时间内消耗，这允许人们访问与饮酒事件的开始和持续相关的回路。所提出的核心有四个目标： 1. 酌情结合使用原位杂交 (ISH) 和免疫组织化学 (IHC) 技术，在 C57BL/6J (B6) 小鼠中绘制与 DID、SHAC、WID 和 IGC 相关的电路图。这些研究将检查是否存在与饮酒事件的开始和维持相关的独特回路。鉴于 B6 小鼠在 INIA-West 中的广泛使用，这些数据将作为主要参考电路。 2. 绘制新的遗传动物模型中的相关回路。对于 DID 和 SHAC，将从异源种群 (HS/Npt) 动物（Crabbe 和 Finn）中培育复制选定品系。获得的数据将与具体目标 1 中获得的结果进行对比。 3. 利用四个模型的遗传和药理学变异，进一步完善与过量乙醇消耗相关的回路。 UO1 的几个应用程序计划研究基本行为模型的变化，以便在解剖和/或分子水平上完善相关电路。这些数据可以与目标 1 和 2 中获得的结果进行对比。重要的是，目标 1-3 必须被视为迭代过程的一部分。核心将开始识别相关电路，研究人员将测试最有希望的目标，这反过来将产生新的模型，从而产生额外的核心活动。该核心还将为所有 INIA-West 研究人员提供（目标 4）用于基因阵列和蛋白质组学分析的组织以及高通量 SNP 基因分型设施。