Mechanisms and Role of Spontaneous Retinal Waves in Visual Development.

视网膜自发波在视觉发育中的机制和作用。

• 批准号: 10366985
• 负责人: Michael C. Crair
• 金额: $ 58.56万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2026-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10366985
• 关键词: Adult; Age; Age related macular degeneration; Amblyopia; Area; Axon; Behavior; Biological; Biological Models; Birth; Brain; Calcium; Cells; Characteristics; Child; Complex; Contrast Sensitivity; Cues; Custom; Development; Electrophysiology (science); Exhibits; Eye; Eye Injuries; Eye diseases; Fragile X Syndrome; Gap Junctions; Genetic; Glaucoma; Glutamates; Growth; Human; Image; Imaging Techniques; In Vitro; Inherited; Instruction; Intervention; Mammals; Maps; Mediating; Microscope; Midbrain structure; Molecular; Motion; Motor; Mus; Neuraxis; Neurodevelopmental Disorder; Neurons; Nose; Pattern; Peripheral; Play; Process; Property; Retina; Retinal Ganglion Cells; Role; Sensory; Shapes; Structure; Techniques; Testing; Time; V1 neuron; Viral; Vision; Visual; Visual Cortex; Visual Pathways; Visual impairment; Visual system structure; Work; autism spectrum disorder; axon guidance; base; cell type; cholinergic; experience; experimental study; extrastriate visual cortex; in vivo; interest; middle age; monocular; neural circuit; neurodevelopment; neuron development; novel; optical imaging; receptive field; recruit; response; segregation; self organization; spatial vision; spatiotemporal; starburst amacrine cell; superior colliculus Corpora quadrigemina; two-photon; vision development; visual map; visual receptive field

PROJECT SUMMARY Experiments in this proposal will advance our understanding of mechanisms responsible for the development of precise neural circuitry in the mammalian brain. Patterned activity is critical for normal development of neural circuits, and deficits in activity-dependent circuit refinement are associated with neurodevelopmental disorders such as Fragile X syndrome, autism, and amblyopia. Amblyopia is the most common cause of monocular visual impairment among young and middle-aged adults, with approximately 3 in 100 children effected. Amblyopia is characterized by a range of deficits in spatial vision, spatial contrast sensitivity, and other tasks. However, the mechanisms of this maladaptation are not well understood. We will employ a broad range of techniques, including molecular biological, cell biological, neuroanatomical, electrophysiological and advanced optical imaging techniques in vitro and in vivo. We focus our experiments on neural circuits in the midbrain superior colliculus and visual cortex of the mouse. Beyond the retina, these areas are the largest visual structures in the brain. The superior colliculus is a sensory motor structure that has emerged as an ideal model system for the examination of neural circuit development and function. The visual cortex is a canonical model system for the study of higher order brain function and development in mammals. It is widely hypothesized that molecular cues are responsible for the establishment of gross brain circuit features, and activity dependent processes subsequently refine these circuits to functional precision. The emergence of visual circuit features before the onset of sensory experience suggests that visual map formation is first initiated by activity-independent mechanisms, such as axon guidance molecules, then refined by pre-vision correlated spontaneous activity, and later maintained and sharpened by visual experience after eye-opening. Spontaneous bursting of retinal ganglion cells results in propagating waves of activity that change with age based on their primary excitatory drive. Initially characterized in vitro, stage I waves occur before birth and are mediated by gap junctions between retinal ganglion cells. Stage II occur from birth until around P10 and are mediated by cholinergic starburst amacrine cells. Stage III waves are glutamatergic in origin, with bipolar cells providing the primary excitatory drive onto retinal ganglion cells from P10 until eye-opening. This project aims to examine the specific spatiotemporal features and the underlying cellular mechanisms by which retinal waves are instructive for the development of higher order circuits and neuronal response properties, in both subcortical and cortical circuits, prior to eye opening.

项目摘要 这项提议的实验将促进我们对负责发展的机制的理解。 哺乳动物大脑中精确的神经回路。模式化活动对于神经系统的正常发育至关重要。 活动依赖性回路改善的缺陷与神经发育障碍有关 例如脆性X综合征、自闭症和弱视。弱视是最常见的原因单眼视觉 在青年和中年人中，大约每100名儿童中就有3名受到影响。弱视是 其特征在于空间视觉、空间对比敏感度和其他任务的一系列缺陷。但 这种适应不良的机制还不清楚。我们将采用广泛的技术， 包括分子生物学、细胞生物学、神经解剖学、电生理学和高级光学 体外和体内成像技术。我们的实验集中在中脑上级的神经回路上 丘和视觉皮层。在视网膜之外，这些区域是视网膜中最大的视觉结构。 个脑袋上级丘是一种感觉运动结构，已成为一种理想的模型系统， 检查神经回路的发育和功能。视觉皮层是一个典型的模型系统， 研究哺乳动物的高级脑功能和发育。人们普遍假设分子线索 负责建立总脑回路特征和活动依赖性过程 随后将这些电路细化到功能精度。视觉电路特征的出现先于 感觉经验的出现表明视觉地图的形成首先是由活动无关的 机制，如轴突引导分子，然后通过视觉前相关的自发活动进行改进， 后来通过睁开眼睛后的视觉体验来保持和锐化。视网膜神经节自发性爆裂 细胞导致活动的传播波，其基于它们的主要兴奋性驱动而随年龄变化。最初 在体外表征，I期波发生在出生前，由视网膜间的缝隙连接介导， 神经节细胞第二阶段从出生到P10左右，由胆碱能星状突无长突介导 细胞阶段III波起源于双极细胞，双极细胞提供主要的兴奋性驱动， 视网膜神经节细胞从P10直到睁眼。这个项目旨在研究特定的时空 特征和潜在的细胞机制，视网膜波是有益的发展， 高阶电路和神经元的反应特性，在皮层下和皮层电路，眼睛之前， 开放后