DEVELOPMENT OF STRIATAL COMPARTMENTALIZATION

纹状体分隔的发展

• 批准号: 3386392
• 负责人: ABIGAIL M SNYDER-KELLER
• 金额: $ 8.3万
• 依托单位: WADSWORTH CENTER
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-01 至 1994-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3386392
• 关键词: acetylcholine; afferent nerve; brain mapping; caudate nucleus; cell type; corpus striatum; developmental neurobiology; dopamine; enkephalins; gamma aminobutyrate; immunocytochemistry; laboratory rat; nervous system transplantation; neuroanatomy; neurotoxins; neurotransmitters; putamen; substance P

A spectrum of diseases, both psychiatric and neurological in nature, involve long term progressive changes that may well begin in the earliest phases of brain development. The symptoms of schizophrenia, Tourette's syndrome, Parkinson's disease and Huntington's chorea, may emerge from defects in the anatomical organization of the basal ganglia that result in disordered neurochemical function. The underlying neuropathology appears to involve the striatum (caudate and putamen), a key structure of the basal ganglia- that is characterized by a dense dopaminergic innervation and a compartmentalized distribution of intrinsic neurons. Studies described here will focus on the development of the anatomical organization of this structure, attempting to dissociate those aspects that are intrinsically specified by the striatal neurons, as opposed to those directed by the ingrowth of dopaminergic afferents that occurs very early in life. The aim of the present proposal is to provide an anatomical basis for understanding how interference with the proper development of this key structure may lead to disordered functioning later in life. As a foundation for studying the behavioral consequences of pathological development, it is necessary to understand the factors involved in guiding the normal development of the striatum. The specific experiments involve a temporal and spatial analysis of the development of several cell types found within the striatum, defined immunocytochemically on the basis of their neurotransmitter phenotype. Experimental manipulations will be made it order to perturb the normal development of the distinctive striatal compartmentalization now known to exist. The effects of early removal of dopamine input on striatal development and organization will be assessed both in vivo and in transplanted striatal tissue. Other rats will be treated in utero with an antimitotic agent timed so as to kill a select population of striatal neurons, and the resultant consequences on the development of other cells and afferents to the striatum assessed. These studies are expected to reveal ways in which genetic defects or neurotoxic insults produce alterations in anatomical development of the striatum that result in long-lasting abnormalities in basal ganglia organization and function.

本质上的一系列疾病，无论是精神病和神经学的疾病 涉及长期进行的渐进变化，很可能是最早开始的 大脑发育的阶段。精神分裂症，图雷特的症状 综合征，帕金森氏病和亨廷顿的舞蹈舞，可能会从 基底神经节的解剖组织缺陷，导致 神经化学功能无序。 潜在的神经病理学出现 涉及纹状体（尾状和梭子），这是基础的关键结构 神经节的特征是致密多巴胺能神经和 内在神经元的分室分布。 描述的研究 这里将重点关注该解剖组织的发展 结构，试图解离这些本质上的这些方面 由纹状体神经元指定，而不是由 生命早期发生多巴胺能传入的生长。 目的 目前的建议是为理解提供解剖学基础 如何干扰该关键结构的适当发展可能导致 在以后的生活中发挥作用。 作为研究病理的行为后果的基础 开发，有必要了解指导的因素 纹状体的正常发育。 具体实验涉及 几种细胞类型的发展的时间和空间分析 在纹状体中发现，根据 他们的神经递质表型。 将进行实验操作 它为扰动独特纹状体的正常发育 现在已知存在的分隔。 早期去除的影响 将评估有关纹状体发展和组织的多巴胺输入 体内和移植的纹状体组织。 其他老鼠会 用抗魔法剂定时在子宫内治疗以杀死选择 纹状体神经元的种群，以及对 评估了其他细胞和传入到纹状体的传入。 这些 期望研究揭示遗传缺陷或神经毒性的方法 侮辱会在纹状体的解剖学发展中发生变化 导致基底神经节组织的长期异常和 功能。