Animal Models Core

动物模型核心

基本信息

批准号：
10062502
负责人：
Venetia Zachariou
金额：
$ 33.23万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-02-15 至 2023-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10062502
关键词：
Advisory Committees Algorithms Animal Model Animals Behavior Behavioral Behavioral Assay Biological Assay Blood Chemical Analysis Blood drug level result Brain Brain region Cell physiology Cells Chromatin Cocaine Cognitive Collaborations Committee Members Complex Continuous Infusion Corticosterone Data Dissection Dominant-Negative Mutation Drug Addiction Ensure Female Fiber Gene Transfer Genes Genetic Genetic Transcription Goals Heroin Human Image Individual Injections Knock-out Link Measurement Measures Mediating Microdissection Modeling Molecular Motivation Mus Mutant Strains Mice National Institute of Drug Abuse Neuroglia Neurons Neurosecretory Systems Opiate Addiction Opioid Pharmaceutical Preparations Photometry Plasma Procedures Process Program Research Project Grants Proteins Psychostimulant dependence RNA Rattus Relapse Research Personnel Resources Rodent Rodent Model Role Running Self Administration Services Specificity Stress Syndrome Testing Viral Vector Work addiction behavior test brain reward regions brain tissue cell type chromatin modification cocaine self-administration cohort drug action drug craving drug relapse experimental study gene function genome-wide heroin use in vivo inhibitor/antagonist injection/infusion interest male mature animal meetings mutant neural circuit neurophysiology novel optogenetics osmotic minipump overexpression small hairpin RNA statistics tool

项目摘要

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.

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和阿片类药物在小鼠和大鼠中的作用，以支持 PPG 建立分子和细胞此类测定包括一些常规行为测试以及更复杂的自我测试。由于很难实施，因此采用广泛的行为方法至关重要。从单一模型甚至有限模型中推断出一些复杂的行为综合症，例如成瘾然后，核心以两种主要方式利用这些行为资源。提供自我注射可卡因或海洛因的啮齿类动物的大脑奖励区域的显微解剖每个项目以及基因和染色质分析核心中的分子细胞表征。 Core 与四个项目中的每一个项目合作，生成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。通过提供一系列基因突变小鼠以及大量载体来实现这一目标病毒介导的基因转移，所有这些都得到了核心突变小鼠和病毒的广泛验证。通常最初生成的向量是为了满足单个项目的特定需求，然后提供给其他项目扩大其应用范围并促进 PPG 整合的项目已成为 PPG 研究人员的主导。产生突变小鼠和病毒载体的领域，这使得选择性操纵给定基因成为可能对成年动物的特定细胞类型和大脑区域感兴趣，从而避免与更多的混淆最后，核心提供先进的神经生理学、光遗传学和纤维。为项目研究人员提供光度测量工具，将改变的分子细胞功能与成瘾直接联系起来- 通过巩固这种行为、小鼠突变体、病毒载体和其他工作。在集中式核心内，我们确保对数据进行严格控制，并促进数据的比较和对比各个项目的实验结果这种整合也具有财务意义，因为我们集中并最大限度地有效利用所需的专业知识。