Neurocircuitry Mapping and Genotyping Core

神经回路图谱和基因分型核心

• 批准号: 7681749
• 负责人: ROBERT J. HITZEMANN
• 金额: $ 25.29万
• 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/7681749
• 关键词: Alcohol consumption; Algorithms; Animal Model; Animals; Area; Behavioral Model; Boutos; Brain; Brain region; Breathing; Breeding; Candidate Disease Gene; Cell Count; Classification; Collaborations; Consensus; Consumption; Cytoskeletal Proteins; Data; Data Set; Dependence; Dimensions; Ethanol; Exhibits; FOS gene; Gene Expression; Genes; Genetic; Genotype; Goals; Heavy Drinking; Homer 1a; Imaging Techniques; In Situ; In Situ Hybridization; Knock-in Mouse; Knock-out; Lesion; Letters; Magnetic Resonance Imaging; Maintenance; Maps; Methods; Microsatellite Repeats; Modeling; Molecular; Mus; Procedures; Process; Proteomics; Quantitative Trait Loci; RNA Interference; Rattus; Recombinants; Research; Research Personnel; Resources; SNP genotyping; Schedule; Series; Site; Site-Directed Mutagenesis; Techniques; Testing; Tissues; Variant; Work; alcohol measurement; base; drinking; experience; interest; mouse model; neuroimaging; novel; sample fixation; tissue processing

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）：在INIA-West联盟中广泛使用了三种过量乙醇消耗的行为模型（DID、SHAC和WID）。第四种模型胃内消耗（IGC）仅用于一个部位，但重要的是提供了一种新的小鼠模型，可能是依赖性诱导的饮酒。该核心的主要目的是提供与这些模型中的每一个相关的回路的标准化评估，以及当通过遗传和/或药理学程序修改模型时这些回路中的变化。以下目标系统地安排了核心的计划活动，从基本模式转向各种模式。从DID、SHAC和WID程序的映射角度来看，其优点在于，乙醇在有限的访问时间段内消耗，这允许人们访问与饮酒事件的开始和继续相关联的回路。拟议的核心有四个目的/目标：1。在C57 BL/6 J（B6）小鼠中，适当地使用原位杂交（ISH）和免疫组织化学（IHC）技术的组合，绘制与DID、SHAC、WID和IGC相关的回路。这些研究将检查是否存在与饮酒事件的启动和维持相关的不同回路。鉴于B6小鼠在整个INIA-West中的广泛使用，这些数据将作为主要参考电路。2.在新的遗传动物模型中绘制相关的电路。对于DID和SHAC，重复选择的品系将从异源原种（HS/Npt）动物（Crabbe和Finn）中繁殖。所获得的数据将与具体目标1中所获得的结果进行对比。3.利用四种模型的遗传和药理学差异，进一步完善与过量乙醇消耗相关的回路。几个UO 1应用程序计划调查的基本行为模型的变化，以完善在解剖和/或分子水平的相关电路。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必须被视为一个迭代过程的一部分。核心将开始识别相关的电路，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。