Functional subtypes of retinal ganglion cell photoreceptors

视网膜神经节细胞感光器的功能亚型

基本信息

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
项目类别：
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

项目摘要

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.

项目概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构成视神经神经。有许多不同类型的视网膜神经节细胞，它们同时传递不同的成分视觉，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经过处理的版本光感受器通过视网膜中的突触输出。一些视网膜神经节细胞含有自己的感光色素（黑视蛋白）并直接对光做出反应。本质上感光的视网膜神经节细胞（ipRGC）发送它们的轴突连接到至少 16 个不同的中央大脑区域，并影响多种行为，例如昼夜节律夹带和瞳孔反射、睡眠、体温和情绪。该提案旨在检查 ipRGC 的功能亚型、它们在视网膜中的位置和密度，以及区分功能组的光响应特性。初步数据表明某些 ipRGC 类型可以根据嵌合间距和独特 mRNA 的表达，将其分为功能亚型，以及 Cre。我们假设 ipRGC 亚型仅限于视网膜的子区域，并且这些亚型内的 ipRGC 有所不同在它们的解剖间距中，它们在中枢突触处释放的神经递质以及特定的光刺激他们回应。我们已经确定了 ipRGC 的独特亚型，仅限于背侧视网膜，表达抑制蛋白，并且在视网膜上均匀分布，表明它们在功能组中对齐。在这个建议，我们将在整个视网膜上绘制各个 ipRGC 亚型的位置，以构建空间图它们的树突以及它们如何相互重叠。我们将测试 ipRGC 的独特 mRNA 表达模式并使用中枢大脑注射来标记不同大脑区域的它们并估计总数 ipRGC 亚型。我们将使用多电极阵列记录来记录数千个 ipRGC 的响应到一系列详细的光刺激，并使用无偏聚类分析来定义其功能组。