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: 10589036
• 负责人: Joshua H Singer
• 金额: $ 42.54万
• 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 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10589036
• 关键词: Action Potentials; Address; Amacrine Cells; Anatomy; Animal Model; Axon; Blindness; Cations; Cells; Cellular Morphology; Cellular Structures; Characteristics; Code; Color; Cone; Contrast Sensitivity; Data; Dendrites; Development; Distal; Electrical Synapse; Electrons; Evaluation; Exhibits; Eye; Face; Foundations; Goals; Human; Image; Individual; Inhibitory Synapse; Interneurons; Knowledge; Lateral; Light; Microanatomy; Modeling; Molecular; Motion; Mus; Neurons; Neurosciences; Output; Pathology; Pathway interactions; Photoreceptors; Physiological; Play; Population; Property; Public Health; RBP4 gene; Research; Retina; Retinal Diseases; Retinal Ganglion Cells; Retinitis Pigmentosa; Rod; Role; Scanning; Shapes; Signal Pathway; Signal Transduction; Stimulus; Structure; Synapses; Synaptic Transmission; Testing; Translating; Variant; Vision; Vision research; Visual; Work; cell type; design; experimental study; fluorophore; ganglion cell; gene therapy; horizontal cell; human model; inhibitory neuron; light gated; light microscopy; luminance; micrography; mosaic; mouse model; neural; neural circuit; neuronal cell body; novel; photoreceptor degeneration; presynaptic; presynaptic neurons; programs; receptive field; response; retinal prosthesis; sensory system; signal processing; spatial integration; synaptic inhibition; treatment strategy; ultra high resolution; visual process; visual stimulus; visual threshold

Project Summary: The broad goal of our research program is to understand how neural circuit function depends on the intrinsic properties of component cells and synapses. The specific goal of this proposal is to determine how synaptic inhibition in inner-retinal circuits shapes responses observed in retinal ganglion cells (GCs), the retinal output channels. This proposal is focused on inhibition in a well-studied inner-retinal circuit: the rod bipolar (RB) cell pathway of the mouse retina, which comprises two central neurons, the ON RB and the AII amacrine cell (AC). The AII distributes the RB signal to several retinal output channels, most significantly the ON α and OFF α and δ GCs, and in the past project period, we identified two novel ACs (nNOS-1 and Rpb4) that provide synaptic inhibition to the RB-AII network. Both of these ACs receive input from the type 6 ON cone bipolar (CB) cell, and the properties of the type 6 CB are thought to generate the contrast-sensitivity and well-characterized nonlinear receptive field of the ON α GC. Therefore, we advance the hypothesis that local contrast in the visual scene best engages these novel inhibitory circuits and that the response properties of nNOS-1 and Rpb4 ACs should be evident in the responses of AIIs and downstream ON α and OFF δ GCs. Our goal is to elucidate cellular properties and responses to physiological stimuli at various stages in the RB pathway to understand the functions of these novel inner retinal circuits. The two specific aims proposed will generate an understanding of how variations in the visual scene modulate signal coding within individual retinal output channels: Aim 1 tests the hypothesis that nNOS-1 ACs exhibit a non-classical receptive field surround that is manifested in the responses of downstream neurons in the retinal circuit; Aim 2 expands our combined anatomical and physiological analyses to resolve how distinct inhibitory circuits converge on GCs and permit coding of unique components of the visual scene. Relevance to Public Health: Understanding how visual stimulus coding is implemented by retinal synapses informs the design of retinal prosthetics and the study of animal models of human retinal diseases. The proposed work clarifies how visual signal processing is modulated at three stages in the retinal network and addresses two goals of the Retinal Diseases Program in the National Plan for Eye and Vision Research: one, it builds on knowledge gained from retinal neuroscience to understand how retinal networks process visual images, and two, it works toward identifying the post photoreceptor neural components of adaptation.

项目摘要：我们的研究计划的广泛目标是了解神经电路的功能 取决于组件细胞和突触的内在特性。该提议的具体目标是 确定视网膜电回路中的突触抑制如何形成视网膜神经节中观察到的反应 细胞（GC），残留输出通道。 该建议的重点是在良好的内视网膜电路中的抑制作用：杆双极（RB）细胞 小鼠视网膜的途径包括两个中央神经元，即RB和AII amacrine细胞 （AC）。 AII将RB信号分布到几个残留的输出通道，最明显的是ONα和 OFFα和δGC，在过去的项目期间，我们确定了两个新型AC（NNOS-1和RPB4） 为RB-AII网络提供突触抑制。这两种AC都从锥体上的6型输入中获得输入 双极（CB）细胞以及6型CB的特性被认为会产生对比度敏感性和 ONαGC的良好表征非线性接受场。因此，我们提出了这样一个假设 视觉场景中的局部对比最能与这些新颖的抑制作用相关，并且反应 NNOS-1和RPB4 AC的性能应作为AII和下游α和下游的响应的证据 OFFδGC。我们的目标是阐明各种细胞特性和对物理刺激的反应 RB途径中的阶段，以了解这些新型内部静止电路的功能。这两个具体 提出的目的将产生了解视觉场景中的变化如何调节信号编码的理解 在单个残差输出通道中：AIM 1检验了NNOS-1 ACS暴露于非古典的假设 在视网膜电路中下游神经元的反应中表现出的围绕围绕的接收场；目的 2扩展了我们的结合解剖学和身体分析，以解决不同的抑制回路 在GC上收集并允许对视觉场景的独特组件进行编码。 与公共卫生的相关性：了解视网膜如何实施视觉刺激编码 突触为视网膜假体的设计和人类视网膜动物模型的研究提供了信息 疾病。提议的工作阐明了如何在三个阶段调制视觉信号处理 视网膜网络并解决视网膜疾病计划的两个目标， 视力研究：第一，它基于从残留神经科学中获得的知识，以了解视网膜 网络处理视觉图像，第二，它致力于识别光感受器中性 适应的组成部分。

项目成果

Voltage-gated Na channels in AII amacrine cells accelerate scotopic light responses mediated by the rod bipolar cell pathway.

• DOI: 10.1523/jneurosci.4212-09.2010
• 发表时间: 2010-03-31
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Tian M;Jarsky T;Murphy GJ;Rieke F;Singer JH
• 通讯作者: Singer JH

Multiple Calcium Channel Types with Unique Expression Patterns Mediate Retinal Signaling at Bipolar Cell Ribbon Synapses.

具有独特表达模式的多种钙通道类型介导双极细胞带突触的视网膜信号传导。

• DOI: 10.1523/jneurosci.0183-22.2022
• 发表时间: 2022
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Zhang,Gong;Liu,Jun-Bin;Yuan,He-Lan;Chen,Si-Yun;Singer,JoshuaH;Ke,Jiang-Bin
• 通讯作者: Ke,Jiang-Bin

Dendro-somatic synaptic inputs to ganglion cells contradict receptive field and connectivity conventions in the mammalian retina.

• DOI: 10.1016/j.cub.2021.11.005
• 发表时间: 2022-01-24
• 期刊: Current biology : CB
• 作者: Grimes WN;Sedlacek M;Musgrove M;Nath A;Tian H;Hoon M;Rieke F;Singer JH;Diamond JS
• 通讯作者: Diamond JS

Mind the Gap Junctions: The Importance of Electrical Synapses to Visual Processing.

注意间隙连接：电突触对视觉处理的重要性。

• DOI: 10.1016/j.neuron.2016.04.007
• 发表时间: 2016
• 期刊: Neuron
• 影响因子: 16.2
• 作者: Demb,JonathanB;Singer,JoshuaH
• 通讯作者: Singer,JoshuaH

Analysis of rod/cone gap junctions from the reconstruction of mouse photoreceptor terminals.

• DOI: 10.7554/elife.73039
• 发表时间: 2022-04-26
• 期刊: ELIFE
• 影响因子: 7.7
• 作者: Ishibashi, Munenori;Keung, Joyce;Morgans, Catherine W.;Aicher, Sue A.;Carroll, James R.;Singer, Joshua H.;Jia, Li;Li, Wei;Fahrenfort, Iris;Ribelayga, Christophe P.;Massey, Stephen C.
• 通讯作者: Massey, Stephen C.