Synaptic Transmission in the Rod Pathway of the Mammalian Retina

哺乳动物视网膜杆状通路中的突触传递

• 批准号: 8463200
• 负责人: Joshua H Singer
• 金额: $ 28.62万
• 依托单位: UNIV OF MARYLAND, COLLEGE PARK
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8463200
• 关键词: Address; Affect; Amacrine Cells; Biological Neural Networks; Brain; Cessation of life; Collection; Disease; Event; Exhibits; Eye; Foundations; Gap Junctions; Goals; Human; Image; Individual; Investigation; Lead; Measures; Mediating; Membrane; Membrane Potentials; Modeling; Molecular; Motion; Mus; Noise; Output; Pathway interactions; Patients; Pattern; Photoreceptors; Point Mutation; Positioning Attribute; Potassium Channel; Public Health; Publishing; Regulation; Retina; Retinal; Retinal Cone; Retinal Degeneration; Retinal Diseases; Retinitis Pigmentosa; Series; Shapes; Signal Transduction; Stimulus; Structure; Study models; Synapses; Synaptic Transmission; Testing; Thalamic structure; Translating; Vertebrate Photoreceptors; Vision; Vision research; Visual; Visual system structure; Work; cell type; detector; ganglion cell; insight; light intensity; luminance; neural circuit; novel; phosphoric diester hydrolase; photoreceptor degeneration; postsynaptic; presynaptic; prevent; programs; relating to nervous system; research study; restoration; retinal neuron; retinal rods; transmission process; treatment strategy; voltage

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

项目摘要：在哺乳动物的视网膜内，AII无链氨氨酸细胞在两者中都可以发挥作用 在产生视网膜输出的大多数平行途径中，杆和锥介导的视觉。所以， 了解AII对于理解内部视网膜内的信号至关重要。该提案包括 两个具体的目标，可以洞悉对AIIS的突触输入和机制的调节 在正常和退化视网膜中塑造AIIS的输出。特定目标1检验假设 RB -AII突触在杆介导的视觉信号传导中具有双重目的：在此条件下 RB途径是输送杆输出的唯一手段，突触是事件检测器。在光线下 足以允许杆介导的信号通过杆孔间隙连接进入锥径的强度， 突触是平均亮度的指标。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AII中产生异常的振荡活性，该研究模型 人类视网膜炎色素（RP）。 与公共卫生相关：色素性视网膜炎（RP），大约影响4,000-5,000中的1个 全球个人（仅在美国，就有100,000名患者）是指一系列视网膜疾病 哪个光感受器死亡（杆紧随锥）。 RD1小鼠是人类RP的既定模型 在其视网膜输出中表现出异常的活性。我们的初步工作，构成了 拟议的工作表明，这种活性是由细胞对AIIS的变化引起的。所以， 拟议的研究产生的结果将提供有关内部视网膜电路的新信息 光感受器变性后的变化，并可能提供对治疗的见解 活动依赖于等待盲疾病治疗的患者视觉系统的变化。 该项目的目的针对国家计划中视网膜疾病计划的三个明确目标 眼睛和视力研究：1）确定视网膜炎治疗的潜在鞭毛策略 颜料，2）对photoreceptor的适应性越来越多地了解 电路）和3）对神经网络中的视网膜细胞相互作用的产生方式增加了解 可以解释为视觉图像的信号。 1