Biology of Photosensitive Ganglion Cells

光敏神经节细胞的生物学

• 批准号: 8721961
• 负责人: David M. Berson
• 金额: $ 35.72万
• 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 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8721961
• 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本质上的生理和功能作用 光敏性视网膜神经节细胞（IPRGC）。目前的建议是调查 IPRGC具有开发视网膜的关键过程。 IPRGC是第一个功能感受器 哺乳动物视网膜，在杆和锥前一周以上产生对光的电响应 感光体足够成熟，可以影响残余输出。在这个年龄，神经节细胞轴突已经 将其中心项目建立和完善大脑的视觉中心。这个过程是 被认为取决于视网膜活动，尤其是扫过的电活动的波浪 内部视网膜。在关键的发育阶段（小鼠的第一个后周），残留波是 由胆碱能（Starburst）无链氨氨酸细胞网络驱动，该网络相互兴奋和神经节 细胞通过烟碱受体。这些»II阶段的视网膜波被认为是免于 由于经典光感受器的不成熟而产生的光学影响。但是，我们的初步 证据表明，光确实确实调节了II期视网膜波的行为，并且这种影响 需要黑色素蛋白，即IPRGC的照相。作为回报，海浪激发了IPRGC。这些 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 对视觉系统开发的影响。此更新应用的主要重点是探索 IPRGC之间双向相互作用的性质，机制和功能含义 和II期视网膜波。该提案的具体目的是：1）确定突触 波动激发黑色素蛋白神经节细胞以及波如何塑造中央的机制 IPRGC的项目； 2）评估IPRGC对剩余波的影响，这些机制 负责这些效果，及其对中央视觉视网膜项目发展的影响 目标。拟议的研究将在野生型和一般修饰的小鼠中进行，并将涉及 残留神经元的体外记录和药物操纵；基因表达分析；和 追踪视网膜项目。这些研究将有助于记录重要的新颖 神经节细胞感光器的功能作用，并将阐明负责其的机制 对其他永久神经元的影响令人惊讶。他们将完善我们对LightDrive的作用的理解 视觉系统开发中的活动，可能会重新考虑可能的影响 早产婴儿视觉系统发展的照明环境。