Integrative Neuroscience Initiative on Alcoholism

关于酗酒的综合神经科学倡议

• 批准号: 7683806
• 负责人: George F. Koob
• 金额: $ 91.58万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-27 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7683806
• 关键词: Alcoholism; Alcohols; Amygdaloid structure; Animal Model; Area; Behavioral; Biological Assay; Brain; Clinical; Core Facility; Dependence; Development; Foundations; Gene Cluster; Gene Targeting; Genes; Genetic; Goals; Heavy Drinking; Human; In Situ Hybridization; Individual Differences; Knock-out; Methods; Modeling; Molecular; Molecular Analysis; Mus; Neurobiology; Neurosciences; Pilot Projects; RNA Interference; Rattus; Research; Research Personnel; Rewards; Site; Structure; Transcend; Transgenic Organisms; Translations; alcohol research; innovation; multidisciplinary; neuroadaptation; programs

This is a competing renewal application for a Consortium for the Integrative Neuroscience Initiative on Alcoholism (INIA)-West (Notice* NOT-AA-06-101) to identify the molecular, cellular, and behavioral neuroadaptations that occur in specific brain neurocircuitries that result in excessive alcohol consumption. More specifically, the focus of this multidisciplinary initiative will be on the molecular and cellular neuroadaptations in the brain reward circuits associated with the extended amygdala and its connections. The overall hypothesis for INIA-West is that genetic differences and/or neuroadaptations in this circuitry are responsible for the individual differences in vulnerability to the excessive consumption of alcohol. The overall goals of INIA-West are to identify the neurocircuitry and neurobiology responsible for excessive alcohol intake, and to provide the foundation to enable translation of the basic neuroscience findings to the human clinical condition. To accomplish these goals, the following Specific Aims are outlined: (1) To identify specific clusters of genes whose expression is regulated by alcohol and which are responsible for INIA-developed models of excessive alcohol consumption, (2) To confirm gene targets nominated by expression assays or other methods, by use of transgenic, knockout, inducible knockouts, site-specific knockouts, RNAi, and in situ hybridization, (3) To attract new and innovative investigators to the field of alcohol research. The structure of INIA-West is envisioned as two domains (Binge and Dependence) that integrate across three levels of analysis: molecular, cellular, neurocircuitry. Distributed Core facilities are proposed that transcend domains and include the Gene Array Cores, Animal Models Cores (rat and mouse) and the Neurocircuitry Cores. Each Domain is comprised of 10-12 U01 proposals and 1-2 Developmental U01 proposals. A Pilot Project program,is proposed to identify exciting new areas of research and the continual recruitment of new investigators to the alcohol field. The INIA program will be directed by an Administrative Core in close cooperation with the Executive Committee, Steering Committee, and with the continual advice of the Scientific Advisory Board.

这是一个竞争性的更新申请，用于整合神经科学倡议联盟， 酒精中毒（INIA）-West（通知 * NOT-AA-06-101），以确定分子、细胞和行为 在特定的大脑神经回路中发生的神经适应，导致过度饮酒。 更具体地说，这一多学科倡议的重点将是分子和细胞 与杏仁核及其连接相关的大脑奖励回路的神经适应。 INIA-West的总体假设是，该回路中的遗传差异和/或神经适应性是 负责的个体差异的脆弱性过度饮酒。整体 INIA-West的目标是确定导致过量酒精的神经回路和神经生物学 摄入量，并提供基础，使基本神经科学的发现，以人类翻译 临床状况为了实现这些目标，概述了以下具体目标：（1）确定具体的 这些基因簇的表达受酒精的调控，并负责INIA的发展。 过量饮酒模型，（2）确认通过表达测定提名的基因靶点，或 其它方法，通过使用转基因、敲除、诱导型敲除、位点特异性敲除、RNAi和在 原位杂交技术，（3）吸引新的和创新的研究人员到酒精研究领域。的 INIA-West的结构被设想为两个领域（狂欢和依赖）， 分析层次：分子、细胞、神经回路。分布式核心设施的建议，超越 结构域，包括基因阵列核心，动物模型核心（大鼠和小鼠）和神经电路 丹每个领域由10- 1 - 2个U 01提案和1-2个发展U 01提案组成。一个试点 项目计划，提出了确定令人兴奋的新的研究领域和不断招募新的 酒精领域的调查员。INIA计划将由一个行政核心领导， 与执行委员会、指导委员会的合作，以及 科学顾问委员会。