Rod and cone signaling pathways in mammalian retina

项目摘要 在这项竞争性续期申请中，我们建议继续并扩大我们对以下方面的调查： 视网膜中的视杆细胞和视锥细胞信号通路， 视网膜神经节细胞（GC）中的感受野（RF）组织。目标是了解 不同类型的小鼠GC在暗视和明视条件下的时空RF特性， 并确定特定的突触通路的适应依赖性差异， GC RF图谱。有两个具体目标。第一个目标是研究线性时空射频 在暗视和明视条件下的各种类型的GC的概况，并确定 在每种类型的GC中的适应依赖性差异的程度，从而获得 小鼠GC类型的综合目录，通过将尖峰响应与非线性 全视野光阶跃、细胞形态和线性时空感受野（RF）， 马赛克轮廓。第二个目标将确定各种杆和锥路径的贡献 GCs的时空RF轮廓，并确定特定的杆和锥的作用 不同类型GC的适应依赖性RF差异的途径。我们将 采用强大、稳定和高通量的多电极阵列（MEA）技术， 传统的单细胞记录方法，结合线性白噪声二进制 棋盘和非线性全场光刺激协议，以研究时空 各种类型GC的RF曲线。我们的研究将提供重要的机制见解 视网膜GC的时空滤波能力和RF组织，可用于 指导未来对健康视网膜回路发育和维持的研究，以及 如在各种疾病状态如视网膜色素变性下的视网膜回路功能障碍， 先天性静止性夜盲症和青光眼。获得的知识将有助于 开发用于视网膜疾病的新基因/药物疗法和用于设计有效的视网膜 假肢装置

PROJECT SUMMARY In this competing renewal application, we propose to continue and extend our investigations on rod and cone signaling pathways in the retina by focusing on synaptic circuits responsible for receptive field (RF) organization in retinal ganglion cells (GCs). The goal is to understand the space-time RF properties of different types of mouse GCs in scotopic and photopic conditions, and to identify specific synaptic pathways underlying the adaptation-dependent differences in GC RF profiles. There are two specific aims. The first aim will study linear space-time RF profiles of various types of GCs in scotopic and photopic conditions, and to determine the degrees of adaptation-dependent differences in each type of GCs, thereby obtaining a comprehensive catalog of mouse GC types by correlating the spike responses to nonlinear whole-field light steps, cell morphology and linear spatiotemporal receptive field (RF) and mosaic profiles. The second aim will determine contributions of various rod and cone pathways to the spatiotemporal RF profiles of the GCs, and to identify the roles of specific rod and cone pathways in the adaptation-dependent RF differences of individual types of GCs. We will employ the powerful, stable and high throughput multielectrode array (MEA) techniques and the conventional single cell recording methods, in conjunction with the linear white-noise binary checkerboard and the nonlinear whole-field light stimulus protocols to study the spatiotemporal RF profiles of various types of GCs. Our research will provide important mechanistic insights onto the spatiotemporal filtering capacity and RF organization of retinal GCs that can be used to guide future investigations on circuit development and maintenance in healthy retinas, as well as on retinal circuit dysfunctions under various diseased states such as retinitis pigmentosa, congenital stationary night blindness and glaucoma. Knowledge obtained will be useful for developing new gene/drug therapies for retinal disorders and for designing effective retinal prosthetic devices.