STRIATAL GLUTAMATE RECEPTORS DURING DEVELOPMENT

发育过程中的纹状体谷氨酸受体

• 批准号: 3087105
• 负责人: LEON S DURE
• 金额: $ 7.78万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-08-01 至 1996-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3087105
• 关键词: NMDA receptors; acetylcholinesterase; autoradiography; carbon; cats; central neural pathway /tract; computer data analysis; corpus striatum; developmental neurobiology; dopamine; dopamine receptor; embryo /fetus; excitatory aminoacid; experimental brain lesion; glutamate receptor; glycine; immunocytochemistry; laboratory rat; ligands; methylphenyltetrahydropyridine; naloxone; neural conduction; neurotransmitters; radionuclides; substantia nigra; tritium

This application proposes a series of experiments to investigate the development of striatal glutamate receptor subtypes in the rat and cat brain. The striatum is known to participate in the planning and execution of movement, and more recently has been found to play a role in cognition, learning, and behavior. Structurally, the striatum is comprised of at least two compartments, the patches and the matrix, which share afferent and efferent connections. The existence of two parallel but distinct circuits provides a capacity for integration and modulation of information both to and from the striatum. To date, the patch and matrix compartments have been defined primarily by immunohistochemical and autoradiographic techniques. The patches appear in the striatum earlier than the matrix, and they are richer in opiate receptors and dopamine than the surrounding matrix. Acetylcholinesterase (AChE) activity is higher in patches than in matrix in fetal and noenatal rat and cat, only to reverse the pattern during aging. The adult rat and cat exhibit AChE-poor patches and AChE-rich matrix. Glutamate is the neurotransmitter of the cortical projections to the striatum, and there is preliminary evidence using quantitative in vitro autoradiography to suggest a patchy distribution of striatal glutamate receptor binding in neonatal rat, adult cat, and in infant and adult human brain. The subtype of glutamate receptor defined by the binding of the excitatory amino acid (EAA) N-methyl-D-aspartate (NMDA) has been shown to have a trophic effect in cortical neuronal development, but has not been investigated in the striatum. To determine the pattern of development of striatal glutamate receptors, neonatal rat and fetal kitten brain will be utilized. Quantitative in vitro receptor autoradiography will be used to determine the time course of appearance of the patch-matrix mosaic of receptor binding of the glutamate receptor subtypes (NMDA, iontrophic quisqualate, metabotropic quisqualate, and kainate). Adjacent brain sections will beassayed for AChE activity to compare the patch-matrix mosaic defined by EAA autoradiography to the mosaic defined immunohistochemically. Finally, lesioning experiments will be done to determine the effect that cortical and nigral connections have on the development of the patch- matrix mosaic of EAA receptors. Neonatal rats and kittens will undergo decortication, and fetal kittens will undergo chemically induced nigral lesions with 6-hydroxy dopamine, followed by receptor autoradiography. These manipulations will provide information regarding the role that cortical and nigral connections to the striatum play in the development of the patch-matrix mosaic.

本申请提出了一系列实验来研究 大鼠和猫纹状体谷氨酸受体亚型的发育 个脑袋 已知纹状体参与计划， 运动的执行，最近已经发现发挥作用， 在认知、学习和行为方面。 在结构上，纹状体是 包括至少两个隔室，贴片和基质， 共享传入和传出连接。 存在两 并行但不同的电路提供了集成的能力， 调节纹状体的信息。 到目前为止，补丁和基质室已被定义主要是 免疫组织化学和放射自显影技术。 贴片 比基质更早出现在纹状体中，并且它们更富含 阿片受体和多巴胺比周围的矩阵。 乙酰胆碱酯酶（AChE）活性在斑片中高于基质 在胎儿和新生大鼠和猫中，只有在 衰老 成年大鼠和猫表现出乙酰胆碱酯酶缺乏和乙酰胆碱酯酶丰富的斑块 矩阵 谷氨酸是大脑皮层投射到大脑皮层的神经递质， 纹状体，并有初步证据表明，使用定量体外 放射自显影显示纹状体谷氨酸的斑片状分布 新生大鼠、成年猫以及婴儿和成人中的受体结合 人脑 谷氨酸受体的亚型定义为 兴奋性氨基酸（EAA）N-甲基-D-天冬氨酸（NMDA）的 显示在皮层神经元发育中具有营养作用，但 尚未在纹状体中进行研究。 为了确定纹状体谷氨酸受体的发育模式， 将使用新生大鼠和胎猫脑。 定量的 体外受体放射自显影将用于确定时间进程 受体结合的斑块-基质镶嵌体的出现 谷氨酸受体亚型（NMDA，离子营养型使君子酸，代谢型 使君子酸盐和红藻氨酸盐）。 将对相邻脑切片进行检测， AChE活性，以比较由EAA定义的斑块-基质镶嵌 放射自显影到化学定义的镶嵌。 最后，将进行损伤实验以确定 皮层和黑质的连接对补丁的发展有什么影响 EAA受体的基质镶嵌。 新生的老鼠和小猫将经历 去皮质，胎儿小猫将经历化学诱导黑质 用6-羟基多巴胺治疗病灶，然后进行受体放射自显影。 这些操作将提供有关作用的信息， 皮质和黑质与纹状体的联系在 镶嵌图的最后一部分