STRIATAL GLUTAMATE RECEPTORS DURING DEVELOPMENT

发育过程中的纹状体谷氨酸受体

• 批准号: 3087104
• 负责人: LEON S DURE
• 金额: $ 7.74万
• 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/3087104
• 关键词: NMDA receptors; acetylcholinesterase; autoradiography; 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; 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.

这个应用程序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 大脑。已知纹状体参与计划和 运动的执行力，最近被发现发挥了作用 在认知、学习和行为方面。从结构上讲，纹状体是 包括至少两个隔室，贴片和基质， 它们共享传入和传出连接。两个人的存在 并行但不同的电路提供了集成和 调制传入和传出纹状体的信息。 到目前为止，已经初步定义了补丁和矩阵隔间 通过免疫组织化学和放射自显影技术。补丁 在纹状体中出现的时间早于基质，而且它们在 阿片受体和多巴胺比周围的基质。 斑块中乙酰胆碱酯酶(AChE)活性高于基质 在胚胎和新生大鼠和猫身上，只有在 衰老。成年大鼠和猫表现出疼痛贫乏斑块和富含疼痛 矩阵。 谷氨酸是大脑皮质投射的神经递质 纹状体，并有初步证据使用体外定量 放射自显影提示纹状体谷氨酸呈斑块状分布 新生大鼠、成年猫以及婴儿和成年猫的受体结合 人脑。谷氨酸受体的亚型由结合决定 在兴奋性氨基酸(EAA)中，N-甲基-D-天冬氨酸(NMDA)已被 被证明对皮质神经元的发育有营养作用，但 未在纹状体内进行研究。 为了确定纹状体谷氨酸受体的发育模式， 将利用新生大鼠和胎猫的大脑。数量输入 体外受体放射自显影将被用来确定时间进程 受体结合的斑块-基质马赛克的出现 谷氨酸受体亚型(NMDA型、离子型、代谢型 Quisqualate和Kainate)。相邻的脑部切片将被检测 比较EAA定义的斑块-基质镶嵌的AChE活性 放射自显影以免疫组织化学方法定义的马赛克。 最后，将进行损伤实验，以确定 皮质和黑质的连接对斑块的发展有影响- EAA受体的基质镶嵌。新生的大鼠和小猫将经历 去皮，胎猫将经历化学诱导的黑质 用6-羟基多巴胺毁损，然后进行受体放射自显影。 这些操作将提供有关角色的信息， 皮质和黑质与纹状体的联系在发育中起作用 斑块矩阵马赛克。