DEVELOPMENT OF NIGROSTRIATAL NEURONAL SYSTEMS

这项研究提案的目的是阐明 纹状体内多巴胺及其相关神经元系统的个体发育 大鼠黑质与黑质之间的相互作用 这些神经系统在发育过程中。这些研究将提供 关于这些系统的正常发展和重要性的信息 这些系统之间在调控和控制方面的相互作用 发展。这项研究的主要假设是 神经递质及其受体在特定的时间段内 开发对于正常的功能开发至关重要 受体和突触后神经元。这项研究将集中在 黑质纹状体多巴胺通路和已知的神经递质系统 在发育过程中或在成年大鼠中与此途径相互作用。一位少校 重点是空间、数量和功能的发展 神经递质受体。该提案有两个主要方面。 首先，神经系统发育的基础研究将继续进行， 集中在神经递质受体和功能 个体神经系统的标志物。特定的受体 这项研究的兴趣是多巴胺d1和d2和乙酰胆碱烟碱 和毒鼠强受体。特定神经元群体的其他标记物 将检查的内容包括多巴胺和DOPAC含量，酪氨酸 羟基酶活性、高亲和力胆碱摄取与胆碱 乙酰转移酶活性。该提案的第二个方面涉及使用 干扰正常发育的程序，例如特定的损伤或 特定的药理试剂，作为进一步检查 神经系统在发育过程中的相互作用。这些因素的影响 对特定神经系统发育的干扰将 被用来调查各种不同的 为彼此的发育提供神经系统。拟议的研究 利用放射自显影作为一种定量方法 决议与生化、药理和分子生物学 允许检查解剖和发育的技术 神经递质系统的功能及其诱发改变的检测 在发展中通过改变正常发展的特定的 系统的一部分。

The objective of this research proposal is to elucidate the stages of ontogeny of dopamine and associated neuronal systems in the striatum and substantia nigra of the rat and to investigate the interactions between these neuronal systems during development. These studies will provide information on normal development of these systems and on the importance of interactions between these systems in regulating and controlling development. The major hypothesis of this study in that the interaction of neurotransmitters with their receptors during a specific time period in development is critical for the normal functional development of the receptors and of the postsynaptic neurons. This study will focus on the nigrostriatal dopamine pathway and on neurotransmitter systems known to interact with this pathway during development or in the adult rat. A major emphasis is the spatial, quantitative and functional development of neurotransmitter receptors. There are two major aspects to the proposal. First, basic studies on the development of neuronal systems will continue, with a concentration on neurotransmitter receptors and on functional markers for individual neuronal systems. The receptors of particular interest in this study are dopamine Dl and D2 and acetylcholine nicotinic and muscarinic receptors. Other markers for specific neuronal populations that will be examined include dopamine and DOPAC content, tyrosine hydroxylase activity, high-affinity choline uptake and choline acetyltransferase activity. The second aspect of the proposal involves use of procedures to perturb normal development, such an specific lesions or specific pharmacological agents, as a further means of examining the interaction of neuronal systems during development. The effects of these perturbations on the development of the particular neuronal systems will be used to investigate the importance of interactions between the various neuronal systems for each other's development. The proposed research utilizes autoradiography as a quantitative approach with very high resolution, together with biochemical pharmacological and molecular biology techniques to allow examination of the development of the anatomy and function of neurotransmitter systems and examination of the change induced in that development by alterations in the normal development of specific part of the system.