Diverse visual processing properties of novel ganglion cell and amacrine cell types in the human retina

项目总结/摘要 我们研究的目的是了解人类视网膜的视觉处理过程。在 提出的工作，我们将探索许多新的细胞类型，我们有惊人的和新颖的视觉特性 最近在人类视网膜中发现的-包括10多种视网膜神经节细胞（RGC）类型， 视觉信息，以及超过10种调节RGC的多轴索无长突细胞（PAC）类型 大面积的活动。我们将开发新的方法来了解它们在自然视觉中的作用。我们将 利用我们庞大而独特的猕猴记录数据库，猕猴是最接近人类的动物模型。 人类，指导我们用珍贵的人体组织进行实验。这项工作是由几个技术 进展：来自人类供体视网膜的新型大规模高密度记录，新型机器学习 在过去的15年里， 多年来，新的分析方法来识别，建模和比较新的细胞类型及其在两种细胞中的功能 物种在这两个物种的初步结果揭示了一个惊人的各种新的RGC和PAC类型，一些 它们可能是同源物，还有一些可能是人类独有的。我们将追求两个目标：（1）确定 猕猴视网膜中许多新的RGC和PAC类型，探测它们不寻常的光响应特性， 开发模型，使我们能够进一步探索它们在自然视觉中的作用，以及（2）识别和表征许多 RGC和PAC类型在人类视网膜，然后使用新的大规模分析方法，以确定 猕猴视网膜中的同源类型。在这项工作结束时，我们将确定并彻底 表征了人类视网膜输出处的许多最重要的视觉通路， 测试模型的功能，在自然视觉，定量比较同系物中最重要的 动物模型，并确定了视网膜细胞类型和视觉信号，这可能是人类独有的。

Project Summary/Abstract The goal of our research is to understand the visual processing performed by the human retina. In the proposed work, we will explore the striking and novel visual properties of numerous new cell types we have recently discovered in the human retina – including more than 10 retinal ganglion cell (RGC) types that send visual information to the brain, and more than 10 polyaxonal amacrine cell (PAC) types that modulate RGC activity over large areas. We will develop new methods to understand their role in natural vision. We will leverage our large, unique database of recordings from macaque monkeys, the animal model closest to the human, to direct our experiments with precious human tissue. This work is made possible by several technical advances: novel large-scale high-density recordings from human donor retinas, novel machine-learning methods for mining of similar large-scale recordings from macaque monkey retinas performed over the last 15 years, and novel analytical methods to identify, model and compare new cell types and their function in the two species. Preliminary results in both species reveal a striking variety of new RGC and PAC types, some of which are likely homologs, and others that may be unique to humans. We will pursue two aims: (1) identify many novel RGC and PAC types in the macaque retina, probe their unusual light response properties, and develop models that allow us to further probe their role in natural vision, and (2) identify and characterize many RGC and PAC types in the human retina, and then use novel large-scale analysis methods to identify homologous types in the macaque retina. At the conclusion of this work, we will have identified and thoroughly characterized many of the most important visual pathways at the output of the human retina, developed and tested models of their function in natural vision, quantitatively compared to homologs in the most important animal model, and identified retinal cell types and visual signals that are likely unique to humans.