Regulation of the intrinsic melanopsin-based light response in ipRGCs

ipRGC 中基于内在黑视蛋白的光响应的调节

• 批准号: 10153790
• 负责人: RONALD Lane BROWN
• 金额: $ 40.29万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-05-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10153790
• 关键词: Address; Animals; Arrestins; Behavior; Behavioral; Binding; Biochemical; Brain; Cell Culture Techniques; Cell physiology; Circadian Rhythms; Cone; Coupled; Cyclic AMP-Dependent Protein Kinases; Data; Electrophysiology (science); Exhibits; Eye; G-Protein-Coupled Receptors; GTP-Binding Protein alpha Subunits, Gs; GTP-Binding Proteins; Goals; Health; Human; Knowledge; Learning; Light; Link; Masks; Measures; Mediating; Memory; Molecular; Moods; Morphology; Mus; Mutant Strains Mice; Opsin; Pathway interactions; Performance; Phospholipase C; Phosphorylation; Phosphotransferases; Photoreceptors; Photosensitivity; Phototransduction; Physiological; Physiology; Play; Post-Translational Protein Processing; Process; Pupil; Pupil light reflex; Regulation; Research; Retina; Retinal Ganglion Cells; Retinal Pigments; Rhodopsin; Role; Signal Transduction; Site; Sleep; Synapses; System; TRP channel; Testing; Vertebrate Photoreceptors; Viral; Vision; Visual system structure; Work; base; behavioral outcome; behavioral response; beta-adrenergic receptor; circadian; circadian regulation; constriction; desensitization; functional outcomes; in vivo; insight; melanopsin; member; mutant; receptor; response; transcription factor

Proposal Summary/Abstract: In the mammalian retina, there is a small subset of retinal ganglion cells (RGCs) that function as autonomous photoreceptors and exhibit light responses independent of rod/cone-driven synaptic input. These intrinsically photosensitive RGCs (known as, ipRGCs) relay light information to the brain to regulate several light-dependent processes, such as circadian photoentrainment, the pupillary light reflex (PLR), sleep, and mood. ipRGCs use the photopigment melanopsin and a G-protein coupled phototransduction cascade to respond to light, and are now known to comprise 5 different subtypes (M1-5) that can be differentiated based on morphological and electrophysiological criteria, projection targets, and transcription factor expression. Currently, there exists a major gap in our understanding of how the regulation of melanopsin and its downstream phototransduction pathways in different ipRGC subtypes govern distinct light-mediated behaviors. Based on our preliminary data, the goal of the proposed research is to determine, in Aim I, the role of melanopsin posttranslational modifications in ipRGC-mediated behaviors in vivo, and in Aim II, the phototransduction components that allow distinct ipRGC subtypes to intrinsically detect light and influence ipRGC-subtype specific behaviors. These studies will provide a critical understanding of the biochemical and molecular mechanisms by which light influences a wide range effects on human health and performance through the regulation of circadian rhythms, sleep, mood, and learning & memory.

提案摘要/摘要： 在哺乳动物视网膜中，有一小部分视网膜神经节细胞（RGCs）具有自主神经功能， 光感受器，并表现出独立于杆/锥驱动的突触输入的光响应。这些本质上 光敏RGC（称为ipRGC）将光信息中继到大脑以调节几种光依赖性的光依赖性神经元。 这些过程包括昼夜光诱导、瞳孔光反射（PLR）、睡眠和情绪。ipRGC使用 所述色素黑视蛋白和G蛋白偶联的光转导级联以响应光， 现在已知包括5种不同的亚型（M1-5），其可以基于形态学和 电生理学标准、投射靶点和转录因子表达。目前，有一个 我们对黑视蛋白及其下游光转导的调节机制的理解存在重大差距 不同ipRGC亚型中的通路支配不同的光介导的行为。根据我们的初步数据， 这项研究的目的是确定黑视素翻译后修饰的作用 在ipRGC介导的体内行为中，以及在Aim II中，允许不同ipRGC的光转导组分 亚型，以内在地检测光并影响ipRGC亚型特异性行为。这些研究将提供 对光影响广泛的生物化学和分子机制的批判性理解 通过调节昼夜节律、睡眠、情绪和学习对人类健康和表现的影响 和记忆。