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主要目的是提供广泛的刺激性行为测定并优化小鼠和大鼠的作用，以支持PPG建立分子和细胞的总体目标成瘾的基础。例如测定包括几个常规行为测试以及更复杂的自我测试管理和继电器程序。使用广泛的行为电池至关重要，因为很难推断出复杂的行为综合征，例如来自单个模型甚至有限的成瘾模型数。然后，核心以两种主要方式利用这些行为资源。首先，核心提供了自我辅助可卡因或海洛因的啮齿动物的大脑奖励区域的微作用每个项目中的分子 - 细胞表征以及基因和染色质分析核心。第二，核心与四个项目中的每个项目一起工作，以生成因果证据，这些证据直接连接特定分子和细胞适应定义成瘾状态的特定行为异常。核心通过提供一系列基因突变小鼠以及大量向量来实现这一目标病毒介导的基因转移，所有这些基因转移均由核心广泛验证。突变小鼠和病毒然后将向量通常生成以满足单个项目的特定需求，然后将其提供给其他项目扩大其应用程序，从而促进PPG集成。 PPG调查人员领导了生成突变小鼠和病毒载体的领域，这使得有可能选择性操纵给定的基因在成年动物的特定细胞类型和大脑区域中感兴趣，从而避免了更多的混淆传统方法。最后，核心提供高级神经生理学，光学遗传学和纤维指向研究人员的光度法工具直接将分子 - 细胞功能与成瘾联系起来 - 相关的行为异常。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核心内，我们确保对数据的严格控制并促进比较和对比各个项目的实验结果。这种整合也很有意义，因为我们集中并最大程度地利用所需的专业知识。