SEROTONIN AND RETINOTECTAL DEVELOPMENT

描述：研究的目标是确定 5-羟色胺（5-HT）是一种在大脑中很早就出现的生物胺 其水平可受两种处方的显著影响 药物和滥用药物，在哺乳动物的发育中起着重要作用。 视网膜顶盖投射 最近的研究结果表明，5-HT 深刻地影响了视网膜顶盖轴突的出生后完善 这可能是5-HT 1B受体介导的作用的结果。 胺对已知参与该过程的活性依赖性机制的影响。 此外，在其他系统中的工作表明，5-HT也可能影响 视网膜顶盖轴突的最初侧支。 拟议 实验将进一步阐明5-HT在视网膜顶盖中的作用， 发展：1）确定视网膜顶盖投影是否是 当5-HT直接应用于上级丘（SC）时发生改变 在整个发展中。 pI会将缓释聚合物芯片 在出生后的前3周用5-HT浸渍SC，然后使用 顺行追踪技术评估视网膜顶盖的组织结构 预测。 2)确定5-HT是否影响视网膜顶盖轴突 通过这种胺对突触传递的影响进行改进。 的 首席研究员将进行体内实验，以确定 非交叉视网膜顶盖的明显增强的精细化 与SC中5-HT浓度降低相关的预测 直接对SC应用TTX可阻断发育。3） 确定5-HT对发育的活动依赖性作用是否 视网膜轴突由5-HT 1B受体介导。 校长 研究者将使用放射性配体结合来确定5-HT 1B受体 第一次出现在发展中的SC和定义的元素，表达 他们 他们还将进行体外生理实验， 5-HT对发育中仓鼠视网膜顶盖传递的影响， 以确定介导细胞凋亡的受体的药理学特征， 这些行动。 他们将评估视网膜顶盖的发育 在缺乏5-HT 1B受体的转基因小鼠中的投射。 4)确定 5-HT浓度的改变是否影响初始侧支化 视网膜顶盖轴突在体内，是否增加浓度， 胺影响离体神经节细胞轴突生长。

DESCRIPTION: The goal of the research is to determine the role that serotonin (5-HT), a biogenic amine that appears very early in brain development and whose levels can be markedly influenced by both prescription medications and drugs of abuse, plays in the development of the mammalian retinotectal projections. Recent results have suggested that 5-HT profoundly influences the postnatal refinement of retinotectal axon arbors and that this may be a result of 5-HT 1B receptor-mediated effects of this amine on activity-dependent mechanisms known to be involved in this process. Moreover, work in other systems has suggested that 5-HT might also influence the initial collateralization of retinotectal axons. The proposed experiments will further elucidate the role of 5-HT in retinotectal development by: 1) Determining whether the retinotectal projection is altered when 5-HT is directly applied to the superior colliculus (SC) throughout development. The pI will place slow release polymer chips impregnated with 5-HT over the SC for the first 3 weeks of life and then use anterograde tracing techniques to assess the organization of retinotectal projections. 2) Determining whether 5-HT influences retinotectal axon refinement through effects of this amine on synaptic transmission. The principal investigator will carry out in vivo experiments to determine whether the apparently enhanced refinement of the uncrossed retinotectal projection associated with a reduced 5-HT concentration in SC during development can be blocked by application of TTX directly to the SC. 3) Determining whether the activity-dependent effects of 5-HT on developing retinal axons are mediated by the 5-HT1B receptor. The principal investigator will use radioligand binding to determine when 5-HT1B receptors first appear in the developing SC and define the elements which express them. They will also carry out in vitro physiological experiments to define the effects of 5-HT on retinotectal transmission in developing hamsters and to determine the pharmacologic profile (s) of the receptor(s) mediating these actions. They will evaluate the development of retinotectal projections in transgenic mice lacking the 5-HT1B receptor. 4) Determining whether altered 5-HT concentration influences the initial collateralization of retinotectal axons in vivo and whether increased concentrations of this amine influence axonal outgrowth from identified ganglion cells in vitro.