SEROTONIN AND RETINOTECTAL DEVELOPMENT

血清素和视网膜发育

• 批准号: 2711178
• 负责人: ROBERT W RHOADES
• 金额: $ 17.98万
• 依托单位: UNIVERSITY OF TOLEDO HEALTH SCI CAMPUS
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2711178
• 关键词: axon; developmental neurobiology; genetically modified animals; hamsters; laboratory rat; retina; serotonin; serotonin receptor; superior colliculus; visual pathways

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.

描述：研究的目的是确定以下角色： 血清素 (5-HT)，一种在大脑中很早就出现的生物胺 其发展及其水平会受到处方的显着影响 药物和滥用药物在哺乳动物的发育中发挥作用 视网膜顶盖投影。 最近的结果表明 5-HT 深刻影响视网膜顶盖轴突轴突的出生后细化 这可能是 5-HT 1B 受体介导作用的结果 胺对已知参与该过程的活性依赖性机制的影响。 此外，其他系统中的工作表明 5-HT 也可能影响 视网膜顶盖轴突的初始侧支。 拟议的 实验将进一步阐明5-HT在视网膜顶盖中的作用 通过以下方式进行开发： 1) 确定视网膜顶盖投影是否为 当 5-HT 直接应用于上丘 (SC) 时发生改变 整个开发过程中。 pI 将放置缓释聚合物芯片 在婴儿出生后的前 3 周内用 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 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细化。 这 首席研究员将进行体内实验以确定 未交叉的视网膜顶盖的细化是否明显增强 与 SC 期间 5-HT 浓度降低相关的预测 可以通过将 TTX 直接应用于 SC 来阻止开发。 3） 确定 5-HT 对发育是否具有活动依赖性影响 视网膜轴突由 5-HT1B 受体介导。 校长 研究人员将使用放射性配体结合来确定 5-HT1B 受体何时 首先出现在发展中的 SC 中并定义了表达的元素 他们。 他们还将进行体外生理实验来定义 5-HT 对发育中仓鼠视网膜顶盖传输的影响 确定介导受体的药理学特征 这些行动。 他们将评估视网膜顶盖的发育情况 缺乏 5-HT1B 受体的转基因小鼠的预测。 4）确定 改变 5-HT 浓度是否会影响初始抵押 体内视网膜顶盖轴突的变化以及该浓度是否增加 胺影响体外确定的神经节细胞的轴突生长。