Animal Models Core

项目摘要/摘要-动物模型核心 动物模型核心的一个主要目标是提供广泛的兴奋剂行为分析 在小鼠和大鼠中的阿片作用，以支持PPG的总体目标，即建立分子和细胞 上瘾的依据。这种分析包括几种常规的行为测试以及更复杂的自我测试 管理和复发程序。使用广泛的行为单元是至关重要的，因为很难 从单一模型甚至有限的模型中推断出复杂的行为综合征，如成瘾 型号的数量。然后，核心通过两种主要方式利用这些行为资源。第一，核心 提供了对啮齿类动物大脑奖赏区域的显微解剖，这些啮齿动物自我给予可卡因或海洛因 每个项目中的分子-细胞特征以及基因和染色质分析核心。第二， CORE与这四个项目中的每一个项目合作，以产生直接联系特定分子和 细胞对定义成瘾状态的特定行为异常的适应。《核心》 通过提供一系列基因突变小鼠以及大量的载体来实现这一目标 病毒介导的基因转移，所有这些都得到了Core的广泛验证。突变小鼠和病毒 向量通常最初是为满足单个项目的特定需求而生成的，然后提供给其他 项目，以扩大它们的应用，从而促进PPG的融合。PPG调查人员领导了 在产生突变小鼠和病毒载体方面，这使得有选择地操纵给定基因成为可能 在成年动物的特定细胞类型和大脑区域内感兴趣，从而避免与更多 传统的方法。最后，核心提供先进的神经生理学、光遗传学和光纤 为项目研究人员提供的光度学工具，将分子细胞功能的改变与成瘾直接联系起来- 相关的行为异常。通过巩固这种行为、小鼠突变、病毒载体和其他工作 在一个集中的核心内，我们确保对数据进行严格控制，并促进 各个项目的实验结果。这种整合在财务上也是有意义的，因为我们 集中并最大限度地有效利用所需的专业知识。

PROJECT SUMMARY/ABSTRACT– ANIMAL MODELS CORE A main objective of the Animal Models Core is to provide a broad range of behavioral assays of stimulant and opiate action in mice and rats to support the PPG’s overall goal to establish the molecular and cellular basis of addiction. Such assays include several routine behavioral tests as well as more sophisticated self- administration and relapse procedures. It is crucial to employ a broad behavioral battery since it is difficult to infer something about a complex behavioral syndrome like addiction from a single model or even a limited number of models. The Core then utilizes these behavioral resources in two main ways. First, the Core provides microdissections of brain reward regions from rodents that self-administer cocaine or heroin for molecular-cellular characterization in each Project and the Gene and Chromatin Analysis Core. Second, the Core works with each of the four Projects to generate causal evidence that directly links specific molecular and cellular adaptations to particular behavioral abnormalities that define a state of addiction. The Core accomplishes this goal by providing a range of genetic mutant mice as well as a large number of vectors for viral-mediated gene transfer, all of which are extensively validated by the Core. The mutant mice and viral vectors, often generated initially to meet the specific needs of an individual Project, are then provided to other Projects to broaden their application and thereby promote PPG integration. PPG investigators have led the field in generating mutant mice and viral vectors, which make it possible to selectively manipulate a given gene of interest within a particular cell type and brain region of adult animals, thus avoiding confounds with more traditional approaches. Finally, the Core provides advanced neurophysiology, optogenetic, and fiber photometry tools to Project investigators to directly relate altered molecular-cellular function to addiction- related behavioral abnormalities. By consolidating this behavioral, mouse mutant, viral vector, and other work within a centralized Core, we ensure rigorous control over the data and facilitate comparisons and contrasts of experimental results across the individual Projects. This consolidation also makes financial sense, since we concentrate and maximize efficient use of the required expertise.