Functional subtypes of retinal ganglion cell photoreceptors

项目摘要 视网膜通过视网膜神经节细胞向大脑传递视觉信息，这些神经节细胞的轴突组成了视觉。 很有胆量。有许多不同类型的视网膜神经节细胞平行地传递不同的成分 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加工后的版本 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含有自己的感光色素 (黑色素)，并直接对光做出反应。固有的光敏性视网膜神经节细胞(IpRGC)将它们的 轴突通向至少16个不同的中央大脑区域，并影响一系列行为，如昼夜节律 夹带和瞳孔反射、睡眠、体温和情绪。 这项建议试图检查ipRGC的功能亚型，它们在视网膜中的位置和密度，以及 区分官能团的光响应特性。初步数据表明，一些ipRGC类型可以 根据它们的镶嵌间距和独特的mRNA表达将其分为功能亚型和Cre。 我们假设ipRGC亚型局限于视网膜的亚区，而这些亚型中的ipRGC不同 在它们的解剖间隔中，它们在中央突触释放的神经递质，以及特定的光刺激 他们对此做出回应。我们已经确定了ipRGC的独特亚型，仅限于表达于视网膜背部的 抑制蛋白在视网膜上均匀分布，表明它们在功能基团中排列一致。在这 建议，我们将绘制整个视网膜上单个ipRGC亚型的位置图，以构建空间地图 它们的树枝状结构以及它们如何相互重叠。我们将测试ipRGCs的独特mRNA表达 并使用中央脑注射从不同的大脑区域标记它们，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作为响应 光刺激的详细阵列，并使用无偏聚类分析来定义其官能团。

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.