Synaptic Transmission in the Rod Pathway of the Mammalian Retina

项目概述：在哺乳动物视网膜内，AII无长突细胞定位于在两个过程中发挥作用。 视杆细胞和视锥细胞介导的视觉在产生视网膜输出的大多数平行通路中。因此，我们认为， 理解AII对于理解内层视网膜内的信号传导至关重要。这项建议包括： 两个具体的目标，将产生深入了解突触输入的调节AIIs和机制， 在正常和退化的视网膜中塑造AIIs的输出。具体目标1检验假设 RB-AII突触在视杆细胞介导的视觉信号传递中起双重作用： RB通路是传递视杆细胞输出的唯一途径，突触起着事件检测器的作用;在光 强度足以允许视杆介导的信号通过视杆-视锥间隙连接进入视锥通路， 突触用作平均亮度的指示器。具体目标2检验了改变K 通道功能在rd 1小鼠视网膜的AIIs中产生异常的振荡活动，rd 1小鼠视网膜是研究的模型 人视网膜色素变性（RP）。 与公共卫生的相关性：视网膜色素变性（RP），约占4，000 - 5，000分之一 全世界的100，000名患者（仅在美国就有100，000名患者），是指在美国的视网膜疾病的集合。 哪些光感受器死亡（视杆细胞随后是视锥细胞）。rd 1小鼠是已建立的人RP模型， 在视网膜输出中表现出异常的模式活动。我们的初步工作，这构成了基础， 这项工作表明，这种活动是由细胞变化引起的，特别是对AIIs。因此，我们认为， 这些研究的结果将为我们提供新的信息， 光感受器变性后的变化，并可能提供深入了解治疗， 等待治疗致盲疾病的患者视觉系统的活动依赖性变化。 该项目的目的是解决国家计划中视网膜疾病方案的三个明确目标 眼睛和视力研究：1）确定治疗视网膜炎的潜在治疗策略 色素沉着，2）增加对感光后适应的理解（即，神经网络增益控制 电路），以及3）增加对神经网络内视网膜细胞相互作用如何产生 可以被解释为视觉图像的信号。 1

Project Summary: Within the mammalian retina, the AII amacrine cell is positioned to function during both rod- and cone-mediated vision within most of the parallel pathways that generate retinal output. Therefore, understanding the AII is a critical to comprehending signaling within the inner retina. This proposal comprises two specific aims that will generate insight into the regulation of synaptic input to AIIs and the mechanisms shaping AIIs' outputs both in the normal and in the degenerating retina. Specific Aim 1 tests the hypothesis that RB - AII synapse serves a dual purpose in rod-mediated visual signaling: under conditions in which the RB pathway is the only means of conveying rod output, the synapse serves as an event detector; at light intensities sufficient to permit rod-mediated signals pass into the cone pathway via rod-cone gap junctions, the synapse serves as an indicator of mean luminance. Specific Aim 2 tests the hypothesis that altered K channel function generates aberrant oscillatory activity in AIIs of the rd1 mouse retina, a model for the study of human retinitis pigmentosa (RP). Relevance to Public Health: Retinitis pigmentosa (RP), which affects approximately 1 in 4,000 - 5,000 individuals worldwide (and 100,000 patients in the US alone), refers to a collection of retinal diseases in which photoreceptors die (rods followed by cones). The rd1 mouse is an established model of human RP and exhibits aberrant patterned activity in its retinal output. Our preliminary work, which forms the foundation for the proposed work, demonstrates that this activity arises from cellular changes to AIIs specifically. Therefore, the results arising from the proposed studies will provide new information about how the inner retinal circuitry changes following photoreceptor degeneration and may provide insight into treatments that will prevent activity-dependent changes in the visual systems of patients awaiting treatment for blinding diseases. The aims of this project address three explicit goals of the Retinal Diseases Program in the National Plan for Eye and Vision Research: 1) determining potential threaputic strategies for treatment of retinitis pigmentosa, 2) increasing understanding of post-photoreceptor adaptation (i.e., gain control in neural circuits), and 3) Increasing understanding of how retinal cellular interactions within neural networks generate signals that are interpretable as visual images. 1