权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Alcohol-induced plasticity within CRF2 microcircuits in distinct amygdala nuclei

不同杏仁核中 CRF2 微电路内酒精诱导的可塑性

基本信息

批准号：
9320150
负责人：
Melissa A Herman
金额：
$ 14.18万
依托单位：
UNIV OF NORTH CAROLINA CHAPEL HILL
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-08-15 至 2017-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9320150
关键词：
Acute Adverse effects Alcohol abuse Alcohol dependence Alcohols Amygdaloid structure Animal Model Animals Association Learning Behavioral Biological Brain Brain region CRF receptor type 1 Cell Nucleus Cells Chronic Clinical Corticotropin-Releasing Hormone Dependence Electrophysiology (science)Elements Ethanol Fright Future Goals Green Fluorescent Proteins Health Individual Inhibitory Synapse Intercalated Cell Interneurons Investigation Lateral Lead Literature Medial Mediating Microdialysis Molecular Mus Neurobiology Neuronal Plasticity Neurons Output Play Population Prevalence Process Property Prosencephalon Reporter Role Signal Transduction Slice Staging Synapses System Testing United States Work alcohol effect alcohol exposure behavioral response cell type chronic alcohol ingestion conditioned fear drinking drug of abuse in vivo information processing neuroadaptation neurobiological mechanism neurotransmitter release social therapeutic development therapeutic target transmission process

项目摘要

DESCRIPTION (provided by applicant): Alcohol abuse represents a major clinical condition in the Unites States and worldwide. Despite the prevalence of alcohol dependence and the well-known adverse effects of chronic alcohol exposure, the neurobiological mechanisms mediating alcohol's effects in the brain are still not fully understood. The challenge of current and future studies is to understand the neurobiological changes that influence tolerance and dependence in motivational systems that lead to chronic drinking. The amygdala is a major component of the brain involved in the motivational effects of drugs of abuse and alcohol in particular. Local inhibition is a key element of this circuitry and a critical component of the behavioral effects of acute and chronic ethanol consumption. Numerous studies on amygdala circuitry have focused on fear and demonstrated a critical role for local microcircuits in the basolateral amygdala (BLA) in the acquisition and expression of conditioned fear (for review, see Ehrlich et. al). Despite the thorough investigation of this circuitry in the fear literature and the common thread of negative association and learned behavioral responses between fear and alcohol dependence, much less is known about how ethanol engages and/or alters specific microcircuits in the amygdala to produce long-lasting behavioral effects. Previous studies in the BLA indicate that acute and chronic ethanol alter excitatory and inhibitory transmission, however studies examining how these changes impact the activity of specific components of amygdala circuitry are lacking. In addition, no studies have employed parallel cellular and whole-animal approaches to assess how the actions of alcohol are integrated into overall amygdala network function. Recent work by our group demonstrated an important role of the CRF1 system in the effects of ethanol on local circuitry in the central amygdala. These studies highlight the cell-type specific effects of ethanol on the CRF1 system within the CeA, however how the CRF1 system fits into the BLA network remains unclear. Thus, the major goals of the current proposal are to employ a combined cellular electrophysiological, neuroanatomical, and in vivo microdialysis approach to 1) characterize CRF1+ and CRF1- neurons in two discrete sub-regions of the BLA, the LA and BM, 2) examine the phasic and tonic inhibitory transmission in these neurons and the sensitivity of that transmission to acute ethanol at both the cellular and intact network level, 3) determine the local functional and long-range anatomical connectivity of CRF1+ and CRF1- neurons in the BLA, and 4) determine the effects of chronic ethanol exposure on the activity of this microcircuitry at a cellular and network level.

描述（由申请人提供）：在美国和世界范围内，酒精滥用是一种主要的临床疾病。尽管酒精依赖的普遍性和众所周知的慢性酒精暴露的不良影响，介导酒精在大脑中的作用的神经生物学机制仍未完全了解。当前和未来研究的挑战是了解影响导致慢性饮酒的动机系统的耐受性和依赖性的神经生物学变化。杏仁核是大脑的一个主要组成部分，它与药物滥用，尤其是酒精的动机效应有关。局部抑制是这一回路的关键要素，也是神经网络行为效应的关键组成部分