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Animal Models Core

动物模型核心

基本信息

批准号：
10306366
负责人：
Venetia Zachariou
金额：
$ 35.83万
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/10306366
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 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 RNA Rattus Relapse Research Personnel Resources Rodent Rodent Model Role Running Self Administration Services Specificity Stimulant 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 injection/infusion interest male mature animal meetings mutant neural circuit neurophysiology novel optogenetics osmotic minipump overexpression small hairpin RNA statistics stimulant dependence 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.

项目总结/摘要-动物模型核心动物模型核心的一个主要目标是提供一个广泛的行为分析的兴奋剂和阿片作用，以支持PPG的总体目标，即建立分子和细胞成瘾的基础。这些分析包括几个常规的行为测试以及更复杂的自我测试。给药和复发程序。采用广泛的行为电池是至关重要的，因为很难从一个单一的模型甚至是有限的模型中推断出一些复杂的行为综合症，比如成瘾，模型的数量。核心以两种主要方式利用这些行为资源。第一，核心提供了啮齿动物大脑奖励区域的显微解剖，这些啮齿动物自我服用可卡因或海洛因，每个项目中的分子细胞表征以及基因和染色质分析核心。二是核心与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特定行为异常的适应，这些行为异常定义了成瘾状态。核心通过提供一系列遗传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的广泛验证。突变小鼠和病毒矢量，通常最初是为了满足单个项目的特定需求而生成的，然后提供给其他项目。扩大其应用范围，从而促进PPG整合的项目。PPG调查人员领导了在产生突变小鼠和病毒载体领域，这使得有可能选择性地操纵给定的基因在成年动物的特定细胞类型和大脑区域内的感兴趣的细胞，从而避免与更多的细胞混淆。传统的方法。最后，核心提供先进的神经生理学，光遗传学和纤维测光工具，项目调查人员直接涉及改变分子细胞功能成瘾- 相关的行为异常通过巩固这一行为，小鼠突变，病毒载体，和其他工作在一个集中的核心，我们确保严格控制数据，并促进比较和对比，在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门知识。