Biology of Photosensitive Ganglion Cells

光敏神经节细胞的生物学

• 批准号: 8334456
• 负责人: David M. Berson
• 金额: $ 36.45万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-02-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8334456
• 关键词: Acetylcholine; Address; Affect; Age; Amacrine Cells; Axon; Behavior; Biology; Brain; Brain region; Cells; Development; Environment; Gene Expression Profiling; Goals; Health; Immune; In Vitro; Lateral Geniculate Body; Light; Lighting; Mediating; Mus; Nature; Neonatal Intensive Care; Nicotinic Receptors; Output; Pattern; Photoreceptors; Physiology; Premature Infant; Process; Retina; Retinal; Retinal Cone; Retinal Ganglion Cells; Retinal Photoreceptors; Role; Shapes; Signal Transduction; Staging; Synapses; Vision; Visual; Visual Pathways; Visual system structure; Work; cholinergic; ganglion cell; light effects; melanopsin; novel; postnatal; response; retinal neuron; retinal rods; segregation; spatiotemporal; superior colliculus Corpora quadrigemina; vision development

The long term goal of this project is to explore the physiology and functional roles of the intrinsically photosensitive retinal ganglion cells (ipRGCs). The present proposal is to investigate the interactions of ipRGCs with key processes in the developing retina. The ipRGCs are the first functional photoreceptors of the mammalian retina, generating electrical responses to light more than a week before rod and cone photoreceptors are mature enough to affect retinal output. At this age, ganglion cell axons are already establishing and refining their central projections to the visual centers of the brain. This process is thought to be dependent on retinal activity, especially the waves of electrical activity that sweep across the inner retina. During a critical developmental stage (first postnatal week in mice), retinal waves are driven by a network of cholinergic (starburst) amacrine cells which excite each other as well as ganglion cells through nicotinic receptors. These ¿Stage II¿ retinal waves have been considered immune from photic influence due to the immaturity of the classical photoreceptors. However, our preliminary evidence shows that light does, in fact, modulate the behavior of Stage II retinal waves and this influence requires melanopsin, the photopigment of ipRGCs. In return, the waves excite ipRGCs. These bidirectional interactions between retinal waves and ipRGCs are unexpected, and have significant implications for visual system development. The central focus of this renewal application is to explore the nature, mechanisms and functional implications of the bidirectional interactions between ipRGCs and Stage II retinal waves. The specific aims of the proposal are: 1) to determine the synaptic mechanisms by which waves excite melanopsin ganglion cells and how the waves shape the central projections of ipRGCs; and 2) to assess the impact of ipRGCs on retinal waves, the mechanisms responsible for these effects, and their impact on development of retinal projections to central visual targets. Proposed studies will be conducted in wildtype and genetically modified mice and will involve in vitro recordings and pharmacological manipulation of retinal neurons; gene expression profiling; and tracing of retinofugal projections. These studies will help to document an important and novel functional role for ganglion cell photoreceptors, and will clarify mechanisms responsible for their surprising influence on other retinal neurons. They will refine our understanding of the role of lightdriven activity in visual system development and may prompt a reconsideration of the possible impact of lighting environments on visual system development in premature human infants.

该项目的长期目标是探索内在的生理学和功能作用 光敏视网膜神经节细胞（ipRGC）目前的建议是研究光敏视网膜神经节细胞（ipRGC）的相互作用。 ipRGC 在视网膜发育中具有关键过程 ipRGC 是第一个有功能的光感受器。 哺乳动物的视网膜，比视杆细胞和视锥细胞早一周多对光产生电反应 光感受器已经足够成熟，可以影响视网膜输出。在这个年龄，神经节细胞轴突已经成熟。 建立和完善他们对大脑视觉中心的中央投射。 据认为取决于视网膜活动，尤其是扫过的电活动波 在关键的发育阶段（小鼠出生后第一周），视网膜波 由胆碱能（星爆）无长突细胞网络驱动，这些细胞相互兴奋以及神经节 细胞通过烟碱受体。第二阶段??视网膜波被认为是免疫的 由于经典光感受器的不成熟，光的影响然而，我们的初步。 有证据表明，光确实可以调节第二阶段视网膜电波的行为，并且这种影响 需要黑视蛋白（ipRGC 的感光色素），作为回报，波会激发 ipRGC。 视网膜波和 ipRGC 之间的双向相互作用是出乎意料的，并且具有显着的意义 该更新应用程序的中心重点是探索对视觉系统开发的影响。 ipRGC 之间双向相互作用的性质、机制和功能含义 该提案的具体目标是： 1) 确定突触。 波激发黑视蛋白神经节细胞的机制以及波如何塑造中央神经节细胞 ipRGC 的预测；2) 评估 ipRGC 对视网膜电波的影响、机制 造成这些效应及其对视网膜投射到中央视觉发育的影响 拟议的研究将在野生型和转基因小鼠中进行，并将涉及 视网膜神经元的体外记录和药理学操作；和 这些研究将有助于记录一个重要且新颖的现象。 神经节细胞感光器的功能作用，并将阐明负责其作用的机制 它们对其他视网膜神经元的惊人影响将加深我们对光驱动作用的理解。 视觉系统发育中的活动，可能会促使人们重新考虑可能的影响 照明环境对早产儿视觉系统发育的影响。