The Role of a Novel Population of Intrinsically Photosensitive Retinal Ganglion Cells in the Dorsal Retina

背侧视网膜中新型本质光敏视网膜神经节细胞群的作用

基本信息

批准号：
10437028
负责人：
Michael Hayden Berry
金额：
$ 5.18万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-07-01 至 2025-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10437028
关键词：
Activities of Daily Living Address Adult Axon Behavior Behavioral Biochemical Biological Clocks Biology Brain Brain region Cell Extracts Cell Nucleus Cell physiology Cells Characteristics Chronic Circadian desynchrony Code Collection Complex Confocal Microscopy Dorsal Electrophysiology (science)Environment Exercise Eye Functional disorder Future Goals Health Homeostasis Hormonal Hour Human body Image Immunosuppression Industrialization Interruption Investigation Lateral Geniculate Body Lead Light Lighting Location Maintenance Mediating Metabolic Diseases Methods Modernization Mood Disorders Mus Neurons Neurotransmitters Output Patients Periodicity Photoreceptors Photosensitivity Phototransduction Physiology Play Population Preparation Regulation Reporter Retina Retinal Cone Retinal Ganglion Cells Role Sampling Signal Transduction Signal Transduction Pathway Sleep Sleep Disorders Societies Techniques Technology Time Travel United States Vertebrate Photoreceptors Viral Visual Visual Fields Visual Perception Work base cancer risk cell type circadian clinically relevant confocal imaging density gamma-Aminobutyric Acid glycine transporter inhibitory neuron luminance melanopsin metabolic rate multi-electrode arrays neurotransmission novel response retinal rods selective expression shift work suprachiasmatic nucleus tool visual information visual process

项目摘要

Project Summary Modern technological changes have lead to circadian misalignment in large portions of the population. This has resulted in increased rates of metabolic, sleep, and mood disorders. The dysfunction is due to the vast range of biological clocks that regulate many aspects of physiology. Entrainment of these clocks is achieved through the light and dark of the day- night cycle sensed by a unique class of photoreceptors in the retina referred to as the intrinsically photosensitive retinal ganglion cells (ipRGCs). Distinct from the rod and cone photoreceptors, which underlie the majority of visual perception, ipRGCs form direct connections to non-visual areas of the brain and exercise bio-synchronous control over many hormonal and neuronal aspects of body function. ipRGC-mediated light/dark entrainment is important for health maintenance and interruptions can lead to endogenous clock dysregulation. This significant health burden demonstrates a clear need for methods of circadian realignment and maintenance. IpRGCs are responsible for encoding changes in ambient light across the entire retina but are far more complex than originally anticipated. Though they only make up 2-5% of the RGC population in the eye, ipRGCs are diverse, consisting of at least 6 distinct subpopulations that project to more than 30 discrete brain regions. While each of these classes express melanopsin, they are thought to have distinct downstream signal transduction pathways. Therefore, each subpopulation is extracting, encoding, and projecting different aspects of visual information in order to influence a separate collection of light-driven behaviors. The specific functional roles of the majority of ipRGC subpopulations remain unclear. To address this shortcoming we will investigate a previously undescribed subpopulation of ipRGCs present only in the dorsal hemisphere of the retina. These ventral-coding ipRGCs express Cre under control of the glycine transporter and are immunopositive for melanopsin and GABA. Their distribution and neurotransmitter type are characteristics that are thus far unique among RGCs. Our goal is to understand their functional sensitivity, central connectivity, and signal transduction pathways. I will do this using electrophysiology in isolated preparations of retina, Cre-dependent viral tracing, and novel photochemical tools. We hypothesize that this dorsally located subpopulation of ipRGCs extract, encode, and project information differently from the greater ipRGC population. This will be the first study describing this novel neuronal population and will serve to generate techniques that can be applied to future investigations in the retina and brain. Artificial light contributes to interference of the biological clocks through the function of the ipRGCs. However, the distribution and inhibitory neurotransmission of this novel subpopulation may suggest that location of light within the visual field is important for regulation. The clinical relevance of this information may lead to location-based methods of realignment in patients suffering from circadian derangements.

项目概要现代技术变革导致大部分人的昼夜节律失调。这导致了新陈代谢、睡眠和情绪障碍的发生率增加。这种功能障碍是由于生物钟范围广泛造成的调节生理学的许多方面。这些时钟的夹带是通过白天的光明和黑暗来实现的—— 视网膜中一类独特的光感受器（称为本质光敏视网膜）感知夜间周期神经节细胞（ipRGC）。与构成大部分视觉感知基础的视杆细胞和视锥细胞光感受器不同， ipRGC 与大脑的非视觉区域形成直接连接，并对许多区域进行生物同步控制。身体功能的荷尔蒙和神经元方面。 ipRGC 介导的光/暗夹带对健康很重要维护和中断可能导致内源性时钟失调。这一重大的健康负担表明显然需要昼夜节律调整和维护的方法。 IpRGC 负责编码整个视网膜环境光的变化，但比原本预计的。虽然 ipRGC 只占眼睛 RGC 总数的 2-5%，但它们是多种多样的，包括至少 6 个不同的亚群投射到 30 多个离散的大脑区域。虽然这些类别中的每一个都表示黑视蛋白，它们被认为具有独特的下游信号转导途径。因此，每个亚群是提取、编码和投影视觉信息的不同方面，以影响单独的集合光驱动的行为。大多数 ipRGC 亚群的具体功能作用仍不清楚。为了解决这个缺点，我们将研究以前未描述的 ipRGC 亚群，该亚群仅存在于视网膜的背半球。这些腹侧编码 ipRGC 在甘氨酸转运蛋白的控制下表达 Cre，并且黑视蛋白和 GABA 免疫阳性。它们的分布和神经递质类型是这样的特征在 RGC 中是独一无二的。我们的目标是了解它们的功能敏感性、中央连接性和信号转导途径。我将使用电生理学在视网膜、Cre 依赖性病毒的分离制剂中做到这一点追踪和新型光化学工具。我们假设这个位于背部的 ipRGCs 提取物亚群，编码和投影信息的方式与更大的 ipRGC 群体不同。这将是第一个描述这一点的研究新的神经元群体，并将有助于产生可应用于未来视网膜研究的技术和大脑。人造光通过 ipRGC 的功能干扰生物钟。然而，这个新亚群的分布和抑制性神经传递可能表明光在视野对于调节很重要。该信息的临床相关性可能会导致基于位置的方法昼夜节律紊乱患者的重新调整。