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递给大脑，视网膜神经节细胞的轴突组成了视觉系统。 神经。存在许多不同类型的视网膜神经节细胞，其平行地传递不同的光化学成分。 视觉，如细节、颜色、方向或强度。大多数视网膜神经节细胞接受的是经过处理的 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含有自己的色素 （黑视素）并直接对光作出反应。视网膜内光敏神经节细胞（ipRGC）将其 轴突到至少16个不同的中央大脑区域，并影响广泛的行为，如昼夜节律 夹带和瞳孔反射、睡眠、体温和情绪。 该提议试图检查ipRGC的功能亚型、它们在视网膜中的位置和密度，以及它们在视网膜中的表达。 光响应特性区分功能组。初步数据表明，一些ipRGC类型可以 根据嵌合体间距和独特mRNA的表达，可将其分为功能亚型，Cre。 我们假设ipRGC亚型仅限于视网膜的亚区域，并且这些亚型内的ipRGC不同。 它们在解剖学上的间距，它们在中央突触释放的神经递质，以及特定的光刺激， 他们回应。我们已经鉴定了ipRGC的独特亚型，其仅限于背侧视网膜，其表达 抑制蛋白，并均匀地分布在整个视网膜上，表明它们在功能组中对齐。在这 根据这项提议，我们将在整个视网膜上绘制单个ipRGC亚型的位置，以构建空间图 它们的树突以及它们是如何重叠的。我们将测试ipRGC的独特mRNA表达， 模式，并使用中央大脑注射来标记它们来自不同的大脑区域， ipRGC亚型。我们将使用多电极阵列记录来记录数千个ipRGC的响应 一个详细的阵列的光刺激，并使用无偏聚类分析，以确定其功能组。