DEVELOPMENT OF NIGROSTRIATAL NEURONAL SYSTEMS

本研究建议的目的是阐明 纹状体中多巴胺能和相关神经元系统的个体发生 和黑质的大鼠，并研究之间的相互作用 这些神经系统在发育过程中。 这将提供信息 这些相互作用在调节和控制神经元 发展 本研究将集中在黑质纹状体多巴胺能神经元 通路和已知与该通路相互作用的神经元系统， 发育或成年大鼠。 该建议有两个方面。 首先，将进行神经系统发育的基础研究， 专注于神经递质受体作为发展的标志， 单个神经元系统。 特别感兴趣的受体是 多巴胺D1和D2、血清素S2、胆碱能毒蕈碱、阿片能μ和 神经降压素受体 还将检查其他标志物，包括 多巴胺含量、高亲和力胆碱摄取和脑啡肽水平。 第二，程序将被用来扰乱特定的正常发展， 系统的一部分。 这些扰动对发展的影响 其他神经元系统的研究将探讨的重要性， 神经系统之间的相互作用，以促进彼此的发展。 这项研究利用定量光学显微镜 放射自显影结合生化药理学技术， 一种允许检查正常发育的方法 神经递质系统和检查引起的变化， 通过干扰正常神经元的相互作用， 以非常高的分辨率进行定量。 这将反过来提供一个 为进一步研究生物外源性物质的影响奠定了基础， 药物或环境污染物，对中央发展 神经系统

The objective of this research proposal is to elucidate the stages of the ontogeny of dopaminergic and associated neuronal systems in the striatum and substantia nigra of the rat and to investigate the interactions between these neuronal systems during development. This will provide information on the role of these interactions in regulating and controlling neuronal development. This study will focus on the nigrostriatal dopaminergic pathway and on neuronal systems known to interact with this pathway in development or in the adult rat. There are two aspects to the proposal. First, basic studies on the development of neuronal systems will be done, concentrating on neurotransmitter receptors as markers for development of individual neuronal systems. The receptors of particular interest are dopamine D1 and D2, serotonin S2, cholinergic muscarinic, opiatergic mu and neurotensin receptors. Other markers will also be examined, including dopamine content, high-affinity choline uptake and enkephalin levels. Second, procedures will be used to perturb normal development of particular parts of the system. The effects of these perturbations on the development of other neuronal systems will be examined to investigate the importance of interactions between the neuronal systems for each other's development. The proposed research utilizes quantitative light microscopic autoradiography combined with biochemical pharmacological techniques as an approach that allows examination of the normal development of neurotransmitter systems and examination of the changes induced in that development by interference with normal neuronal interactions in a quantitative manner at very high resolution. This will, in turn, provide a basis for further studies on the effects of xenobiotic agents, such as drugs or environmental pollutants, on the development of the central nervous system.