Role of mammalian retinal photoreceptors in non-image-forming visual functions

哺乳动物视网膜感光器在非成像视觉功能中的作用

• 批准号: 9188814
• 负责人: HAIQING ZHAO
• 金额: $ 39.25万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-20 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9188814
• 关键词: Ablation; Acute; Address; Animals; Behavior; Biological Clocks; Body Temperature; Brain; Brain region; Circadian Rhythms; Cognition; Complex; Darkness; Data; Dependence; Detection; Electrophysiology (science); Eye; Functional disorder; Funding; Genetic; Glutamates; Goals; Health; Human; Image; Impairment; Individual; Lead; Light; Mammals; Mediating; Mental Depression; Metabolic; Molecular; Moods; Morphology; Mus; Nature; Neurons; Neuropeptides; Neurotransmitters; Other Genetics; Pathway interactions; Photoreceptors; Photosensitivity; Phototransduction; Physiologic pulse; Physiology; Population; Pupil light reflex; Quality of life; Regulation; Retina; Retinal; Retinal Ganglion Cells; Retinal Photoreceptors; Role; Signal Pathway; Signal Transduction; Sleep; Sleep disturbances; Synapses; Testing; Vertebrate Photoreceptors; Vision; Wild Type Mouse; base; behavior influence; cell type; fast-acting neurotransmitter; ganglion cell; light effects; melanopsin; neurotransmission; pituitary adenylate cyclase activating polypeptide; public health relevance; response; retinal rods

DESCRIPTION (provided by applicant): Light has profound influences on many non-image forming (NIF) visual functions including circadian rhythms, sleep, mood, body temperature and the pupillary light reflex. In mammals, light influences these NIF functions through three retinal photoreceptors, namely the classical photoreceptors, rods and cones, and the intrinsically photosensitive retinal ganglion cells (ipRGCs), which express the photopigment melanopsin. As ganglion cells, ipRGCs integrate rod/cone input with their own intrinsic melanopsin-based phototransduction to serve as the sole conduits to signal light information to brain regions important for these NIF functions. However, how ipRGCs, a seemingly "homogeneous" population, integrate extrinsic light input from rods and cones with their own intrinsic melanopsin-based light responses to coordinate diverse behaviors is poorly understood. The overall goal of this competitive renewal is to address this fundamental question at three levels. In Aim I, we will determine the functional circuits by which rod, cone and melanopsin-based signals are integrated in ipRGCs to drive NIF functions. Recently, we found that ipRGCs are much more diverse than previously appreciated, consisting of multiple morphologically and electrophysiologically distinct subtypes. Additionally, ipRGCs appear to be unique among retinal ganglion cells in that they co-express two neurotransmitters, glutamate and a neuropeptide, PACAP. Thus, in Aim II, we will define the relative contribution of glutamatergic and peptidergic neurotransmission to diverse NIF functions. In Aim III, we will elucidate the functional contribution of individual ipRGC subtypes to NIF functions. These studies will advance our current understanding of the role of ipRGCs in controlling light- mediated behaviors that are essential to human health and a better quality of life.

描述（由申请人提供）：光对许多非成像（NIF）视觉功能具有深远的影响，包括昼夜节律、睡眠、情绪、体温和瞳孔对光反射。在哺乳动物中，光通过三种视网膜感光器影响这些 NIF 功能，即经典感光器、视杆细胞和视锥细胞，以及表达感光色素黑视蛋白的本质感光视网膜神经节细胞 (ipRGC)。作为神经节细胞，ipRGC 将视杆细胞/视锥细胞输入与其自身固有的基于黑视蛋白的光转导结合起来，作为向对这些 NIF 功能重要的大脑区域发出光信息的唯一管道。然而，ipRGCs作为一个看似“同质”的群体，如何将来自视杆细胞和视锥细胞的外在光输入与它们自身基于黑视蛋白的内在光响应相结合以协调不同的行为，人们知之甚少。此次竞争性更新的总体目标是在三个层面上解决这一基本问题。在目标 I 中，我们将确定基于视杆、视锥和黑视蛋白的信号在 ipRGC 中集成以驱动 NIF 功能的功能电路。最近，我们发现 ipRGC 比以前认识的更加多样化，由多种形态和电生理学不同的亚型组成。此外，ipRGC 在视网膜神经节细胞中似乎是独特的，因为它们共表达两种神经递质：谷氨酸和神经肽 PACAP。因此，在目标 II 中，我们将定义谷氨酸能和肽能神经传递对不同 NIF 功能的相对贡献。在目标 III 中，我们将阐明各个 ipRGC 亚型对 NIF 功能的功能贡献。这些研究将增进我们目前对 ipRGC 在控制光介导行为方面的作用的理解，这些行为对于人类健康和更好的生活质量至关重要。