Functional subtypes of retinal ganglion cell photoreceptors

视网膜神经节细胞感光器的功能亚型

• 批准号: 10367719
• 负责人: Benjamin M Sivyer
• 金额: $ 43.83万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-04-01 至 2027-01-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10367719
• 关键词: Anatomy; Antibodies; Area; Axon; Behavior; Body Temperature; Brain; Brain region; Cells; Classification; Cluster Analysis; Code; Color; Cone; Confocal Microscopy; Data; Dendrites; Detection; Disease; Dorsal; Enzymes; Eye; Functional disorder; Health; Image; Individual; Injections; Label; Laboratories; Light; Location; Malignant Neoplasms; Maps; Measures; Mental Depression; Messenger RNA; Metabolic syndrome; Moods; Morphology; Mosaicism; Mus; Mydriasis; Neuropeptides; Neurotransmitters; Optic Nerve; Output; Pathway interactions; Pattern; Photons; Photoreceptors; Photosensitivity; Physiological; Physiology; Process; Property; Proteins; Pupil; Reflex action; Retina; Retinal Ganglion Cells; Reverse Transcriptase Polymerase Chain Reaction; Sampling; Signal Transduction; Sleep; Stains; Stimulus; Stratification; Synapses; Syndrome; System; Territoriality; Testing; Transgenic Mice; Vision; Visual; Visual Fields; Visual system structure; Work; base; cell type; circadian; density; experimental study; functional group; luminance; mRNA Expression; melanopsin; multi-electrode arrays; neurotransmission; neurotransmitter release; novel; postsynaptic neurons; reconstruction; response; transcriptome; visual information; visual processing

Project Summary The retina conveys visual information to the brain through retinal ganglion cells whose axons make up the optic nerve. There are many different types of retinal ganglion cells that in parallel convey a different component of vision, such as detail, color, direction, or intensity. Most retinal ganglion cells receive a processed version photoreceptor output, through synapses in the retina. Some retinal ganglion cells contain their own photopigment (melanopsin) and respond directly to light. Intrinsically photosensitive retinal ganglion cells (ipRGCs) send their axons to at least 16 distinct central brain regions and influence a wide range of behaviors such as circadian entrainment and pupil reflex, sleep, body temperature, and mood. This proposal seeks to examine functional subtypes of ipRGCs, their location and density in the retina, and the light response properties that differentiate functional groups. Preliminary data indicates some ipRGC types can be divided into functional subtypes based on their mosaic spacing and the expression of unique mRNA, and Cre. We hypothesize ipRGC subtypes are restricted to sub-regions of retina and ipRGCs within these subtypes differ in their anatomical spacing, the neurotransmitters they release at central synapses, and the specific light stimuli they respond to. We have identified unique subtypes of ipRGCs with restricted to the dorsal retina that express inhibitory proteins and are spaced evenly across the retina, indicating they align in functional groups. In this proposal, we will map the locations of individual ipRGC subtypes across the entire retina to build a spatial map of their dendrites and how they overlap with each other. We will test ipRGCs for unique mRNA expression patterns and use central brain injections to label them from distinct brain regions and estimate the total number of ipRGC subtypes. We will use multielectrode array recordings to record from thousands of ipRGCs in response to a detailed array of light stimuli and use unbiased cluster analysis to define their functional groups.

项目摘要 视网膜通过视网膜神经节细胞将视觉信息传达给大脑的视觉信息，其轴突构成了光学 神经。有许多不同类型的视网膜神经节细胞并行传达 视觉，例如细节，颜色，方向或强度。大多数视网膜神经节细胞都会收到处理的版本 光感受器输出，通过视网膜中的突触。一些视网膜神经节细胞包含其自己的照片动作 （黑色素蛋白）并直接响应光。本质上光敏性的视网膜神经节细胞（IPRGC）发送其 至少16个不同的中央大脑区域的轴突，并影响各种行为，例如昼夜节律 夹带和学生反射，睡眠，体温和情绪。 该建议旨在检查IPRGC的功能性亚型，它们在视网膜中的位置和密度以及 区分官能团的光响应特性。初步数据表明某些IPRGC类型可以 根据其镶嵌间距和独特mRNA和CRE的表达，将其分为功能性亚型。 我们假设IPRGC亚型仅限于这些亚型内的视网膜和IPRGC的子区域 在解剖学间距中，它们在中央突触中释放的神经递质和特定的光刺激 他们回应。我们已经确定了IPRGC的独特子类型，其中仅限于表达背侧视网膜 抑制性蛋白质，并在整个视网膜上均匀地间隔，表明它们在官能团中排列。在这个 提案，我们将在整个视网膜上绘制单个IPRGC子类型的位置，以构建空间地图 他们的树突及其如何相互重叠。我们将测试IPRGC的独特mRNA表达 模式并使用中央大脑注射将它们从不同的大脑区域标记并估算总数 IPRGC子类型。我们将使用多电极阵列记录来录制数千个IPRGC的响应 进行详细的光刺激阵列，并使用无偏的聚类分析来定义其功能组。