DEVELOPMENT OF NIGROSTRIATAL NEURONAL SYSTEMS

本研究计划的目的是阐明 纹状体中多巴胺和相关神经元系统的个体发生， 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。这些研究将提供 关于这些系统的正常发展以及 这些系统之间的相互作用， 发展本研究的主要假设是， 在特定的时间段内， 发展是至关重要的正常功能的发展， 受体和突触后神经元。本研究将集中于 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该途径相互作用。一个主要 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，关于神经系统发育的基础研究将继续进行， 集中于神经递质受体和功能性 单个神经元系统的标记。特定的受体 本研究中感兴趣是多巴胺D1和D2以及乙酰胆碱烟碱 和毒蕈碱受体。特定神经元群体的其他标志物 包括多巴胺和DOPAC含量，酪氨酸 羟化酶活性、高亲和力胆碱摄取和胆碱 乙酰转移酶活性建议的第二个方面涉及使用 干扰正常发育的程序，如特定的病变或 特定的药理学试剂，作为检查 发育过程中神经系统的相互作用。成效为何 对特定神经系统发育的干扰将 可以用来研究各种因素之间相互作用的重要性 神经系统的相互发展。拟议研究 利用放射自显影作为定量方法， 以及生化药理学和分子生物学 技术允许检查解剖结构的发展， 神经递质系统的功能和检查引起的变化 通过改变特定细胞的正常发育 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.