DEVELOPMENT OF STRIATAL COMPARTMENTALIZATION

纹状体分隔的发展

• 批准号: 2247120
• 负责人: ABIGAIL M SNYDER-KELLER
• 金额: $ 8.35万
• 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 1995-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2247120
• 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.

一系列疾病，包括精神疾病和神经疾病， 涉及长期渐进的变化，很可能最早就开始 大脑发育的阶段。精神分裂症、抽动秽语症的症状 综合症、帕金森病和亨廷顿舞蹈病可能来自 基底神经节解剖组织的缺陷导致 神经化学功能紊乱。 潜在的神经病理学出现 涉及纹状体（尾状核和壳核），这是基底层的关键结构 神经节-其特点是密集的多巴胺能神经支配和 内在神经元的区室化分布。 研究描述 这里将重点关注这个解剖组织的发展 结构，试图分离那些本质上的方面 由纹状体神经元指定，而不是由纹状体神经元指导 生命早期发生的多巴胺能传入神经的向内生长。 目的 本提案的目的是为理解提供解剖学基础 干扰这一关键结构的正常发展会如何导致 导致以后生活功能紊乱。 作为研究病理行为后果的基础 发展过程中，有必要了解影响指导的因素 纹状体的正常发育。 具体实验涉及 几种细胞类型发育的时间和空间分析 在纹状体中发现，根据免疫细胞化学定义 他们的神经递质表型。 将进行实验操作 它是为了扰乱独特纹状体的正常发育 现在已知存在分区化。 早期去除的影响 将评估多巴胺对纹状体发育和组织的输入 在体内和移植的纹状体组织中。 其他老鼠将会 在子宫内用抗有丝分裂剂进行处理，定时以杀死选择的 纹状体神经元的数量，以及对纹状体神经元的影响 评估其他细胞和纹状体传入神经的发育。 这些 预计研究将揭示遗传缺陷或神经毒性的方式 损伤会导致纹状体解剖学发育发生改变 导致基底神经节组织的长期异常 功能。