DRUG MECHANISM IN NEURONAL DOPAMINE ORGANIZATI0N

中枢多巴胺（DA）神经元 发展轴突，并与它们的神经元建立功能性连接。 纹状体（CS）和额叶皮质（FCx）中的靶细胞， 以及这种连接在细胞存活中的作用， 这些细胞的发育神经生物学问题。 这 一个实验室用一种新的方法研究了这些发育问题。 体外分离的细胞再聚集系统，其中单细胞 从胚胎小鼠的特定区域制备的悬浮液 大脑可以自行重组或与细胞重组 其他特定的大脑区域。 只有当与细胞共培养时 从CS或FCx等靶区，DA神经元是否 广泛的轴突过程，并表现出增强的生存。 这 对DA神经元发育的靶细胞依赖性作用与 与靶细胞的膜结合因子。 一个 用于鉴定和表征这些的免疫学策略 描述了利用局部细胞系的神经营养因子。 使用这样的细胞系衍生有重要的优点， 从这些靶细胞作为抗原来源，用于产生 针对因子的特异性抗体。 均匀 永生细胞系提供了几乎无限的启动 材料，它们可能富含这些因素， 与构成原代细胞的异质细胞群相比， CS和FCx细胞。 其他细胞系来源于原代 含有DA的神经元与神经母细胞瘤细胞系产生了 杂交细胞系产生的DA浓度相当于 在成年人的纹状体中发现。 的进一步表征 这些含DA的杂交细胞系相对于 神经递质合成和神经递质受体是一个 这些细胞移植到失神经大鼠的前奏 CS试图扭转相关的行为异常 多巴胺能去神经，Parkison的动物模型， 疾病 最后，DA能神经元的功能组织， 与CS的GABA能靶细胞的关系将用 药理学工具 靶细胞D-1和D-2的个体发育 受体允许发展，单独，或在存在一个 将检查发展中的多巴胺能神经支配。 这些DA 神经系统是药理学的重要作用部位， 代理商，这些实验应该产生进一步的信息， 它们的正常发育是细胞和化学物质的功能， 这种发展的环境。

The manner in which central dopamine (DA)-containing neurons develop axons and establish functional connections with their target cells in the corpus striatum (CS) and frontal cortex (FCx), and the role of such connections in cell survival, are important issues in the developmental neurobiology of these cells. This laboratory has examined these developmental problems using an in vitro, dissociated cell-reaggregation system in which single cell suspensions prepared from specific areas of the embryonic mouse brain are allowed to reaggregate either by themselves or with cells from other specific brain regions. Only when cocultured with cells from target areas such as the CS or FCx do the DA neurons elaborate extensive axonal processes and exhibit enhanced survival. This target cell-dependent effect on DA neuron development is associated with membrane-bound factor(s) of the target cells. An immunological strategy for identifying and characterizing these neuronotrophic factor(s) utilizing local cell lines is described. There are important advantages to using such cell lines derived from these target cells as a source of antigens for generating the specific antibodies directed against the factor(s). Homogeneous immortal cell lines provide practically unlimited starting material, and they are likely to be enriched in these factors compared to the heterogeneous cell population constituting primary CS and FCx cells. Other cell lines derived from fusions of primary DA-containing neurons with a neuroblastoma cell line have produced hybrid cell lines that produce DA in concentrations equivalent to those found in the adult striatum. A further characterization of these DA-containing hybrid cell lines with respect to neurotransmitter synthesis and neurotransmitter receptors is a prelude to the transplantation of such cells into denervated rat CS in an attempt to reverse the behavioral abnormalities associated with dopaminergic denervation, an animal model of Parkison's disease. Finally, the functional organization of DA neurons in relation to GABAergic target cells of the CS will be assessed with pharmacological tools. The ontogeny of target cell D-1 and D-2 receptors allowed to develop, alone, or in the presence of a developing dopaminergic innervation will be examined. These DA neuronal systems are important sites of action for pharmacologic agents, and these experiments should yield further information on their normal development as a function of the cellular and chemical environment in which such development occurs.