Neuronal ensembles of compulsive alcohol drinking

强迫性饮酒的神经元群

基本信息

批准号：
9367885
负责人：
Olivier George
金额：
$ 43.54万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-08-01 至 2022-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9367885
关键词：
Acute Address Alcohol consumption Alcohol dependence Alcohols Amygdaloid structure Behavior Control Brain Brain region Cell Nucleus Chronic Corticotropin-Releasing Hormone Development Event FOS gene Heavy Drinking Hyperalgesia Hypothalamic structure Immediate-Early Genes Investigation Knowledge LacZ Genes Lateral Lead Literature Mediating Methods Motivation Neurobiology Neurons Pain Pathway interactions Pharmacogenetics Pharmacology Phenotype Population Rattus Recruitment Activity Role Saccharin Self Administration Structure of terminal stria nuclei of preoptic region Techniques Testing Time Transgenic Organisms Withdrawal alcohol exposure anxiety-like behavior design experimental study improved negative emotional state neurobiological mechanism neuronal circuitry novel optogenetics parabrachial nucleus prevent tool vapor

项目摘要

Project Summary/Abstract A key issue in the alcohol field is the lack of knowledge on the discreet neuronal ensembles that are responsible for excessive alcohol drinking in alcohol-dependent subjects. This is a major obstacle for the alcohol field because investigations of the neuronal ensembles that mediate excessive alcohol drinking would provide a comprehensive understanding of the neuronal circuits that causally contribute to alcohol dependence. The recent development of pharmacogenetic and optogenetic tools that allow selective targeting of specific neuronal ensembles is a tremendous opportunity to bridge this gap in the literature. The central hypothesis of this proposal is that activation of the parabrachial nucleus (PBN) and central nucleus of the amygdala (CeA) during withdrawal is responsible for the recruitment of a set of discreet neuronal ensembles that are scattered throughout the brain and ultimately responsible for excessive drinking and the emergence of negative emotional states in dependent rats. We obtained robust preliminary results that show that selectively targeting these neuronal ensembles produces long-lasting reversal of excessive alcohol drinking in dependent rats, identifies a causal relationship between these ensembles, and reveals novel neuronal pathways that contribute to alcohol dependence. Specific Aim 1 characterizes the role of the CeA and PBN withdrawal neuronal ensembles in excessive alcohol drinking in dependent rats. Specific Aim 2 dissects the role of the different CeA CRF pathways in the recruitment of the neuronal ensembles and excessive alcohol drinking in alcohol dependence. Results from these studies have the potential to have a strong and lasting impact in the field because our approach will improve our understanding of the neurobiological mechanisms of alcohol dependence and identify novel neuronal populations and circuits that specifically control behaviors associated with alcohol dependence.

项目摘要/摘要酒精领域的一个关键问题是缺乏对谨慎的神经元合奏的知识负责在酒精依赖受试者中过量饮酒。这是酒精场是因为神经元合奏的投资超过饮酒的介导提供对有效促进酒精的神经元电路的全面理解依赖。最新的药物遗传学和光遗传学工具的开发，允许选择性靶向特定的神经元合奏是在文献中弥合这一差距的巨大机会。中央该提议的假设是激活副核核心（PBN）和中央核心撤回期间的杏仁核（CEA）负责招募一组谨慎的神经元合奏散布在整个大脑中，最终负责多余的饮酒和出现依赖大鼠的负面情绪状态。我们获得了强大的初步结果，这些结果表明针对这些神经元的合奏会产生持续的过量饮酒的持续逆转大鼠确定这些集合之间的因果关系，并揭示了新的神经元途径有助于酒精依赖。具体目标1是CEA和PBN退出的作用神经元在依赖大鼠中饮用过量饮酒。特定目的2剖析了在招募神经元合奏和过量酒精中，不同的CEA CRF途径酒精依赖。这些研究的结果有可能对领域，因为我们的方法将改善我们对酒精神经生物学机制的理解依赖性并识别专门控制与之相关的行为的新型神经元种群和电路与酒精依赖。