SEROTONIN AND RETINOTECTAL DEVELOPMENT

血清素和视网膜发育

• 批准号: 2888513
• 负责人: ROBERT W RHOADES
• 金额: $ 18.52万
• 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 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2888513
• 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 5-羟色胺（5-HT），一种在大脑早期出现的生物胺 开发以及其水平可以受到两种处方的明显影响 滥用药物和药物，在哺乳动物的发展中发挥作用 视网膜直肠预测。 最近的结果表明5-HT 深刻影响视网膜直肠轴突轴承的产后细化 这可能是由于5-HT 1B受体介导的作用的结果 胺依赖于已知参与此过程的机制。 此外，其他系统的工作表明5-HT也可能影响 视网膜直肠轴突的初始抵押。 提议 实验将进一步阐明5-HT在视网膜直肠上的作用 开发作者：1）确定视网膜直肠投影是否为 当直接应用5-HT上的5-HT上的上丘（SC）时发生了变化 整个发展。 PI将放置缓慢释放的聚合物芯片 在生命的前三周，在SC上浸渍了5-HT，然后使用 顺行追踪技术，以评估视网膜直肠的组织 预测。 2）确定5-HT是否影响视网膜直直透明轴突 通过该胺对突触传播的影响的细化。 这 主要研究者将进行体内实验以确定 未划线的视网膜直截止是否明显增强 与SC中5-HT浓度降低相关的投影 可以通过将TTX直接应用于SC来阻止开发。 3） 确定5-HT的活性依赖性影响 视网膜轴突由5-HT1B受体介导。 校长 研究者将使用放射性配体结合来确定何时5-HT1B受体 首先出现在开发SC中，并定义表达的元素 他们。 他们还将进行体外生理实验以定义 5-HT对发育中的仓鼠和 确定受体介导的药理谱 这些行动。 他们将评估视网膜直肠的发展 缺乏5-HT1B受体的转基因小鼠的投射。 4）确定 5-HT浓度改变是否会影响初始抵押 体内的视网膜直直直直截止轴突以及是否增加了浓度 胺在体外影响鉴定出神经节细胞的轴突产物。

项目成果

Neonatally elevated serotonin levels alter terminal arbors of individual retinal ganglion cells in superior colliculus of hamsters.

新生儿血清素水平升高会改变仓鼠上丘中单个视网膜神经节细胞的末端乔木。

• DOI: 10.1002/cne.1117
• 发表时间: 2001
• 期刊: The Journal of comparative neurology
• 作者: Crnko-Hoppenjans,TA;Mooney,RD;Rhoades,RW
• 通讯作者: Rhoades,RW

Increased serotonin in the developing superior colliculus affects receptive-field size of retinotectal afferents but not that of postsynaptic neurons.

发育中的上丘中血清素的增加会影响视网膜顶盖传入神经的感受野大小，但不会影响突触后神经元的感受野大小。

• DOI: 10.1017/s0952523899161078
• 发表时间: 1999
• 期刊: Visual neuroscience
• 影响因子: 1.9
• 作者: Ke,M;Mooney,RD;Rhoades,RW
• 通讯作者: Rhoades,RW

Organization of the corticotectal projection in hamsters with neonatally elevated levels of serotonin in the superior colliculus.

新生儿上丘血清素水平升高的仓鼠皮质顶盖投射的组织。

• DOI: 10.1016/s0304-3940(99)00813-7
• 发表时间: 1999
• 期刊: Neuroscience letters
• 影响因子: 2.5
• 作者: Crnko-Hoppenjans,TA;Yaggie,J;Mooney,RD;Rhoades,RW
• 通讯作者: Rhoades,RW

Augmentation of serotonin in the developing superior colliculus alters the normal development of the uncrossed retinotectal projection.

正在发育的上丘中血清素的增加改变了未交叉的视网膜顶盖投射的正常发育。

• 发表时间: 1998
• 期刊: The Journal of comparative neurology.
• 作者: Mooney,RD;Crnko-Hoppenjans,TA;Ke,M;Bennett-Clarke,CA;Lane,RD;Chiaia,NL;Rhoades,RW
• 通讯作者: Rhoades,RW