Synaptic Transmission in the Rod Pathway of the Mammalian Retina

项目摘要：在哺乳动物的视网膜内，AII无长突细胞的定位是在 在产生视网膜输出的大多数平行通路中，视杆和视锥介导的视觉。因此， 理解AII对于理解视网膜内部的信号是至关重要的。这项建议包括 两个具体目标将有助于洞察AIIs突触输入的调节及其机制 在正常和退化的视网膜中塑造AIIs的输出。《特定目标1》检验了假设 Rb-AII突触在视杆介导的视觉信号中具有双重作用：在 RB通路是传递杆状输出的唯一途径，突触起到事件探测器的作用；在光 足以允许棒介导的信号通过棒-锥间隙连接进入锥路径的强度， 突触是平均亮度的指示器。《特定目标2》检验了改变K的假设 通道功能在Rd1小鼠视网膜的ALI中产生异常的振荡活动，这是本研究的一个模型 人类视网膜色素变性(RP)。 与公共卫生相关：视网膜色素变性(RP)，大约每4,000-5,000人中就有1人患病 全球个人(仅在美国就有100,000名患者)，指的是全球视网膜疾病的集合 哪些感光器死亡(视杆后跟着视锥)。Rd1小鼠是已建立的人类RP和 在其视网膜输出中表现出异常的图案化活动。我们的初步工作，这构成了 拟议的工作表明，这一活动特别是由AII的细胞变化引起的。因此， 拟议中的研究结果将提供有关视网膜内部电路如何 光感受器退化后的变化，并可能为预防 等待致盲疾病治疗的患者视觉系统的活动依赖性变化。 这个项目的目标是解决国家计划中视网膜疾病方案的三个明确目标 眼科和视力研究：1)确定潜在的治疗视网膜炎的策略 色素，2)增加对光感受器后适应(即，神经获得控制)的理解 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的理解 可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