BASAL GANGLIA CIRCUITRY IMMEDIATE EARLY GENE EXPRESSION

基底神经节回路立即早期基因表达

• 批准号: 2807476
• 负责人: DAVID WIRTSHAFTER
• 金额: $ 15.96万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-12-01 至 2003-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2807476
• 关键词: basal ganglia; behavioral genetics; central neural pathway /tract; cholinergic receptors; corpus striatum; dopamine; dopamine agonists; dopamine receptor; drug administration routes; experimental brain lesion; fos protein; gene induction /repression; genetic markers; immunocytochemistry; innervation; laboratory rat; microinjections; neuroanatomy; neurogenetics; neuronal transport; neuropharmacology; regulatory gene; transcription factor

DESCRIPTION: (from Abstract) The long term objective of the current proposal is the attainment of a greater understanding of the functional organization of the basal ganglia. Substantial evidence suggests that many neurological and psychiatric disorders, including Parkinson's disease, Huntington's disease, Sydenham's chorea, torsion dystonia, Tourette's syndrome and schizophrenia, may result from abnormalities in the activity of these nuclei. Progress in understanding the etiology of these disorders, and in developing treatments for them, is largely dependent on advances in understanding the basic nature of basal ganglia functioning. The proposed experiments are designed to examine basal ganglia by using the immunocytochemical detection of immediate early genes (IEGs) as markers for neurons affected by various behavioral or pharmacological manipulations. The striatum is the largest nucleus within the basal ganglia and is the primary terminus of input into this system. The first set of studies will examine the pharmacological and behavioral control of IEG expression within this structure with emphasis on the patterning of IEG expression with respect to the striosome/matrix compartmentation of the striatum. The striatum contains a number of neuroactive compounds including dopamine, serotonin, adenosine, acetylcholine and substance P and the role played by these substances in controlling striatal IEG expression will be examined. The applicants will also examine the role of dopamine in IEG expression induced by shuttling behavior and characterize the cells that express IEGs under these conditions. Events occurring within the striatum can only influence behavior by affecting the activity of neurons within other parts of the brain. The second group of studies will therefore use IEG expression as a tool to investigate the basic organization of extrastriatal circuitry related to the basal ganglia. Experiments will examine the ability drugs microinjected directly into the striatum, or other basal ganglia nuclei, to influence IEG expression at extrastriatal sites. Other studies will examine the effects of lesions within the basal ganglia on the IEG expression induced by systemic administration of dopaminergic drugs.

描述：（摘要）当前的长期目标 提案是对功能的更深入的了解 基底神经节的组织。大量证据表明 许多神经和精神病，包括帕金森氏症 疾病，亨廷顿氏病，Sydenham的唱片，扭曲肌张力障碍， 图雷特综合症和精神分裂症可能是由于异常 这些核的活性。理解病因的进展 这些疾病以及为他们开发治疗方面的疾病主要是 取决于理解基底神经节的基本本质的进步 功能。提出的实验旨在检查基础 神经节使用立即立即进行免疫细胞化学检测 基因（IEG）作为受各种行为或影响神经元的标记 药理操作。纹状体是最大的核 在基底神经节内，是输入的主要终点 系统。第一组研究将检查药理学和 在这种结构中对IEG表达的行为控制，重点 关于IEG表达的曲折/矩阵的模式 纹状体的隔室。纹状体包含许多 神经活性化合物，包括多巴胺，5-羟色胺，腺苷， 乙酰胆碱和物质P以及这些物质起作用的作用 在控制纹状体时，将检查IEG表达。申请人 还将检查多巴胺在IEG表达中的作用 穿梭行为并表征在下面表达IEG的单元格 这些条件。纹状体内发生的事件只能 通过影响其他神经元的活动来影响行为 大脑的一部分。因此，第二组研究将使用IEG 表达作为研究基本组织的工具 层外回路与基底神经节有关。实验会 检查直接注入纹状体的能力药物，或 其他基底神经节核，以影响层外IEG表达 站点。其他研究将研究病变的影响 全身给药引起的IEG表达的基底神经节 多巴胺能药物。