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本质上的生理和功能作用 光敏性视网膜神经节细胞（IPRGC）。 IPRGC具有开发视网膜的关键过程。 哺乳动物视网膜，在杆和锥前一周以上产生电气响应 感光体成熟以影响视网膜输出。 建立并将其中心预测到大脑的视觉中心。 被认为是视网膜活动，尤其是电动作用山雀的波浪 内部视网膜。 由胆碱能（Starburst）无链氨氨酸细胞的网络驱动，彼此激发和神经节激发 细胞通过烟碱受体。第二阶段视网膜波被认为免于 由于经典光感受器的不成熟而产生的光学影响 证据表明，光实际上确实是模块化的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 视网膜波和IPRGC之间的双向相互作用是出乎意料的，并且已经表示 对视觉系统开发的影响。 IPRGC之间的性质，机制和功能性含义的含义相互作用 和II期视网膜波。 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的预测； 2）评估视网膜波的IPRGC 负责效果以及对中央视觉视网膜预测的发展的影响 靶标研究将在野生型和转基因小鼠中进行 体外记录和视网膜神经元的药理学； 追踪视网膜预测。 神经节细胞感光器的功能作用，并将对其负责其的机制进行分类 对其他视网膜神经元的影响很大。 视觉系统开发中的活动，并可能促使可能影响可能的影响 早产婴儿视觉系统发展的照明环境。