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FUNCTIONAL MECHANISMS OF THE CORPUS STRIATUM

纹状体的功能机制

基本信息

批准号：
3410037
负责人：
ROBERT M BECKSTEAD
金额：
$ 12.37万
依托单位：
MEDICAL UNIVERSITY OF SOUTH CAROLINA
依托单位国家：
美国
项目类别：
财政年份：
1989
资助国家：
美国
起止时间：
1989-04-01 至 1993-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3410037
关键词：
adrenergic agents antiadrenergic agents cats cell population study cell type corpus striatum dopamine dopamine receptor immunocytochemistry in situ hybridization laboratory rat neural transmission neurochemistry neurons neurotransmitter metabolism

项目摘要

The mechanisms by which nigrostriatal dopamine (DA) transmission engages the corpus striatal circuitry and ultimately affects its output have been of cardinal interest for several years because of the role of DA in extrapyramidal movement disorders and certain derailments of cognitive function in humans. In the past decade, receptor-binding studies, immunohistochemical studies on the distributions of some neuroactive peptides and transmitter-related enzymes, and anatomical studies of striatal inputs have suggested a high degree of compartmentation in the striatum. Moreover, striatal outputs have been distinguished on anatomical and neurochemical grounds and display at least at least a dual organization that is correlated with the different functional roles of the corpus striatal output structures. The actions of DA within the striatum can be mediated by at least two classes of DA receptor termed D1 and D2. The problem of how DA transmission, mediated by these tow classes of DA receptor, influences chemically and connectionally distinct neurons in the various striatal compartments, and how these compartmentalized cell populations relate to one another, and to distinct striatal inputs and outputs is the focus of the proposed anatomical-pharmacological research projects. We will use a quantitative, radioimmunocytochemical technique as well as standard immunocytochemical, radioligand- binding, in situ hybridization and experimental neuroanatomical techniques, alone and in combination, and drug manipulations with selective D1 and D2 agonists and antagonists to assess these relationships in the mammalian brain. The studies will be done in adult cats and rats. These studies will shed light on the manner in which DA released from nigrostriatal terminals interacts with DA receptors and, consequently, neurochemically distinct striatal output pathways. More generally, the increased understanding of functional mechanisms within the corpus striatum will contribute to the scientific basis for the study of clinical disorders associated with corpus striatal dysfunctions.

黑质纹状体多巴胺（DA）传递的机制参与纹状体回路，并最终影响其几年来，产量一直是主要利益，因为 DA在锥体外系运动障碍中作用人类认知功能的脱轨。在过去十年中，受体结合研究，免疫组织化学研究，一些神经活性肽和递质相关的分布酶和纹状体输入的解剖学研究表明，纹状体的高度分隔此外，委员会认为，纹状体输出在解剖学和神经化学的理由，并显示至少有双重与不同职能角色相关的组织纹状体的输出结构。 DA内部的行动纹状体可由至少两类DA受体介导称为D1和D2。多巴胺如何通过这两类DA受体，化学影响，不同的纹状体神经元以及这些分隔的细胞群相互关联，并与不同的纹状体输入和输出是解剖药理学研究的重点项目我们将使用定量放射免疫细胞化学技术以及标准免疫细胞化学、放射性配体- 结合、原位杂交和实验神经解剖学技术，单独和组合，以及药物操作，选择性D1和D2激动剂和拮抗剂，以评估这些哺乳动物大脑中的关系。这些研究将在成年猫和老鼠这些研究将揭示其中黑质纹状体末梢释放的DA与多巴胺受体，因此，神经化学上不同的纹状体输出路径。更普遍的是，纹状体内的功能机制将有助于临床疾病研究的科学基础与纹状体功能障碍有关