Neurocircuitry Mapping and Genotyping Core

描述(由申请人提供)：在整个INIA-WEST联盟中，广泛使用三种过度乙醇消耗的行为模型(DID、SHAC和WID)。第四种模型胃内饮酒(IGC)只在一个地点使用，但重要的是提供了一种新的小鼠模型，很可能是依赖诱导的饮酒。该核心的主要目的是提供与这些模型中的每一个相关的电路的标准化评估，以及当这些模型被遗传和/或药理学程序修改时这些电路中的变化。以下目标系统地安排了核心的有计划的活动，从基本模型到模型的变化。从DID、SHAC和WID程序的映射角度来看，优点是乙醇在有限的访问周期中消耗，这允许人们访问与饮酒事件的开始和继续相关的电路。建议的核心有四个目的/目标：1.适当地结合原位杂交(ISH)和免疫组织化学(IHC)技术，在C57BL/6J(B6)小鼠中定位与DID、SHAC、WID和IGC相关的回路。这些研究将检验是否存在与饮酒发作的启动和维持相关的明显回路。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定位相关回路。对于DID和SHAC，复制选定的品系将从异源种群(HS/NPT)动物(Crabbe和Finn)中培育出来。获得的数据将与在特定目标1.3中获得的结果进行对比。利用四个模型上的遗传和药理学差异来进一步精炼与过量酒精消耗有关的回路。几个UO1应用程序计划研究基本行为模型的变化，以便在解剖学和/或分子水平上改进相关电路。这些数据可以与目标1和目标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，调查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。该核心还将提供(目标4)用于基因阵列和蛋白质组学分析的组织，并为所有INIA-WEST研究人员提供高吞吐量的SNP基因分型设施。

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.