FUNCTIONAL MECHANISMS OF THE CORPUS STRIATUM

黑质纹状体多巴胺(DA)传递的机制 参与纹状体环路，并最终影响其 几年来，产量一直是人们最关心的问题，因为 多巴胺在锥体外系运动障碍中的作用 人类认知功能的脱轨。在过去的十年里， 受体结合研究，免疫组织化学研究 几种神经活性多肽及其递质相关物质的分布 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， 纹状体的输出在解剖学和 神经化学基础和表现至少是双重的 与不同职能角色相关的组织 纹状体纹状体的输出结构。DA在内部的行动 纹状体至少可由两类DA受体介导。 命名为d1和d2。DA如何传播的问题，由 这两类多巴胺受体，在化学上和 不同纹状体中连接不同的神经元 以及这些分隔的细胞群体是如何被分隔的 相互关联，并与不同的纹状体输入和输出相关 是拟议的解剖-药理学研究的重点 项目。我们将使用一种定量的，放射免疫细胞化学 技术以及标准的免疫细胞化学、放射配基- 结合、原位杂交与实验神经解剖学 技术，单独和组合，以及药物操纵与 选择性的D1和D2激动剂和拮抗剂来评估这些 哺乳动物大脑中的关系。这些研究将在#年进行。 成年猫和老鼠。这些研究将阐明这种方式 其中黑质纹状体终末释放的DA与 DA受体，因此，在神经化学上不同的纹状体 输出路径。更广泛地说，对 纹状体内的功能机制将有助于 为临床疾病的研究奠定科学基础 与纹状体功能障碍有关。

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.