Trophic interactions during visual system development

视觉系统发育过程中的营养相互作用

• 批准号: 6927834
• 负责人: SUSANA COHEN-CORY
• 金额: $ 30.5万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6927834
• 关键词: Xenopus; axon; brain derived neurotrophic factor; confocal scanning microscopy; electron microscopy; electrophysiology; green fluorescent proteins; microinjections; neurogenesis; retinal bipolar neuron; synaptogenesis; video microscopy; visual pathways

DESCRIPTION (provided by applicant): The proposed studies will examine the mechanisms by which retinal projection neurons make precise and functional connections with their central targets. The hypothesis that neurotrophic factors modulate optic axon arborization, and synapse formation and stabilization will be tested in the live developing brain. Specifically, the cellular and molecular mechanisms by which the neurotrophin brain-derived neurotrophic factor (BDNF) controls axon and dendritic arborization, and synapse formation/stabilization will be examined in live, anesthetized tadpoles. The Xenopus laevis visual system offers a uniquely accessible vertebrate model in which the development of neuronal connections can be followed over time in the intact embryo. Embryologic manipulations and in vivo imaging techniques (time-lapse confocal microscopy and calcium imaging techniques) will be combined to follow, in real time, the morphological differentiation of pre- and post-synaptic partners and the formation of synaptic connections between the retina and its target optic tectum. By imaging individual optic axon terminal arbors and/or tectal neuron dendritic arbors while simultaneously visualizing synaptic sites in the intact animal, the following hypotheses will be tested: BDNF modulates activity-dependent competition between developing retinal inputs by promoting synapse stabilization between optic axons and target tectal neurons. Target-derived BDNF directly influences optic axon terminals to modulate axon arborization and synapse formation. The BDNF-elicited changes in optic axon arbor complexity lead to structural changes in tectal neuron synaptic complexity. BDNF induces localized changes in intracellular calcium levels in arborizing optic axons that are responsible for synapse stabilization and the formation of new branches. The results of these studies will provide valuable insights into fundamental mechanisms of synaptogenesis in the living brain, and will further our understanding of the mechanisms that control the development of visual pathways, that are critically important in the maintenance of normal visual function.

描述（由申请人提供）：拟议的研究将研究视网膜投影神经元与其中心目标建立精确和功能连接的机制。神经营养因子调节视神经轴突的假设以及突触形成和稳定的假设将在活发育的大脑中进行测试。具体而言，神经营养蛋白脑衍生的神经营养因子（BDNF）控制轴突和树突含量的细胞和分子机制，并将在现场检查，麻醉的tadpoles中检查突触形成/稳定。 Xenopus laevis视觉系统提供了一个独特的脊椎动物模型，其中可以随着时间的推移在完整的胚胎中遵循神经元连接的发展。胚胎学操作和体内成像技术（延时共聚焦显微镜和钙成像技术）将合并，以实时遵循突触前和突触后伴侣的形态分化，以及视网膜及其目标光学疗法之间的突触连接的形成。通过对单个视轴突末端轴和/或张直肠神经元树突状乔木进行成像，同时可视化完整动物中的突触部位，将测试以下假设： BDNF通过促进视觉轴突和靶标直肠神经元之间的突触稳定来调节活性依赖性竞争。 目标衍生的BDNF直接影响视神经轴突终端，以调节轴突木器化和突触形成。 BDNF引起的视轴突轴突复杂性的变化导致构件神经元突触复杂性的结构变化。 BDNF诱导细胞内钙水平的局部变化，用于使突触稳定和新分支的形成的光轴突造成的光轴突。 这些研究的结果将为活大脑中突触发生的基本机制提供宝贵的见解，并将进一步了解控制视觉途径发展的机制，这些机制对于维持正常视觉功能至关重要。