Retinal mechanisms for direction selectivity

视网膜的方向选择性机制

• 批准号: 9392418
• 负责人: Robert G Smith
• 金额: $ 41.28万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-12-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9392418
• 关键词: Adult; Affect; Alpha Cell; Amacrine Cells; Biological Models; Blindness; Brain; Calcium Channel; Cells; Complex; Computer Simulation; Consensus; Darkness; Data; Dendrites; Development; Electrophysiology (science); Environment; Eye; Eye diseases; Feedback; Goals; Human; Image; In Vitro; Interneurons; Knowledge; Label; Light; Measures; Mediating; Methods; Modeling; Morphology; Motion; Movement; Mus; Neurons; Noise; Ocular Prosthesis; Oryctolagus cuniculus; Output; Physiological; Preparation; Process; Property; Prosthesis; Research; Research Project Grants; Retina; Retinal; Retinal Ganglion Cells; Saccades; Signal Transduction; Sodium Channel; Source; Speed; Synapses; Testing; Visual; Width; Work; base; cell type; extrastriate visual cortex; gamma-Aminobutyric Acid; ganglion cell; improved; motion sensitivity; neural circuit; neuromechanism; novel therapeutics; object motion; presynaptic; receptive field; response; species difference; starburst amacrine cell; stimulus sensitivity; synergism; temporal measurement; visual stimulus; voltage; Adult; Affect; Alpha Cell; Amacrine Cells; Biological Models; Blindness; Brain; Calcium Channel; Cells; Complex; Computer Simulation; Consensus; Darkness; Data; Dendrites; Development; Electrophysiology (science); Environment; Eye; Eye diseases; Feedback; Goals; Human; Image; In Vitro; Interneurons; Knowledge; Label; Light; Measures; Mediating; Methods; Modeling; Morphology; Motion; Movement; Mus; Neurons; Noise; Ocular Prosthesis; Oryctolagus cuniculus; Output; Physiological; Preparation; Process; Property; Prosthesis; Research; Research Project Grants; Retina; Retinal; Retinal Ganglion Cells; Saccades; Signal Transduction; Sodium Channel; Source; Speed; Synapses; Testing; Visual; Width; Work; base; cell type; extrastriate visual cortex; gamma-Aminobutyric Acid; ganglion cell; improved; motion sensitivity; neural circuit; neuromechanism; novel therapeutics; object motion; presynaptic; receptive field; response; species difference; starburst amacrine cell; stimulus sensitivity; synergism; temporal measurement; visual stimulus; voltage

Project summary This project proposes to study mechanisms of synaptic processing within specific ganglion cell types in the mammalian retina, both by direct electrophysiological recording and through the use of realistic computer models. Retinal ganglion cells are the output neurons of the retina. There are around 20-30 types of retinal ganglion cell in a typical mammalian retina, with each type optimized to detect different features in the visual scene. Each retinal ganglion cell type is present as an orderly array of cells that cover the entire retina, and therefore the concerted activity of each ganglion cell type represents a separate version of the visual image. Thus, the brain simultaneously receives 20-30 distinct images that it combines within central visual areas to produce a continuous, coherent model of the visual world. This project focuses on a specific type of retinal ganglion cell that signals direction of motion, called the direction-selective ganglion cell (DSGC). Recordings from DSGCs from in-vitro isolated retina preparations in mouse and rabbit will be used to characterize the electrical and morphological properties of these cells. Realistic computational models of the neural circuitry will be generated based on this information. Recapitulation of the real responses by the model system will be used to test our understanding of the underlying neural circuits. The study comprises three sections. Aim 1 examines the function of the starburst amacrine cell (SBAC), an interneuron that is the source of direction selective inhibitory inputs to the DSGC. This aim tests the hypothesis that several mechanisms in SBAC dendrites generate and amplify the direction-selective inhibitory signal. The computer model of the SBAC circuit will include sodium and calcium channels in a network of SBACs that are interconnected by reciprocal inhibition. Aim 2 tests the hypothesis that surround inhibition modulates the strength and spatial and temporal resolution of the synaptic input to the DSGC. The experimental results will be used to extend the computer model to take into account the inhibitory inputs from amacrine cells that integrate information over larger regions of the visual scene surrounding the DSGC. Aim 3 examines the reliability in the spiking output of the DSGC, and how this is affected by the presence of ambiguities and noise in the visual input. The data obtained will be used to further develop the computer model to simulate DSGC spike responses. The final model, based on physiological results from all three Aims, will represent a detailed, and essentially complete representation of the neural mechanisms involved in directional signalling in the mammalian retina. If successful, the model should reproduce realistic spiking output for any visual stimulus. Overall, the proposed research will improve our understanding of the complex circuitry of the adult retina; the knowledge gained will inform continuing efforts to develop treatments and visual prosthetic devices that restore vision loss from a range of eye diseases.

项目摘要 该项目建议研究特定神经节细胞类型中突触加工的机制 哺乳动物视网膜，无论是直接电生理记录还是通过使用逼真的计算机 型号。视网膜神经节细胞是视网膜的输出神经元。大约有20-30种视网膜 典型的哺乳动物视网膜中的神经节细胞，每种类型都优化以检测视觉中的不同特征 场景。每种视网膜神经节细胞类型都作为覆盖整个视网膜的有序细胞阵列，并且 因此，每个神经节细胞类型的协同活动代表视觉图像的单独版本。 因此，大脑同时收到20-30个不同的图像，在中央视觉区域内结合 产生视觉世界的连续，连贯的模型。该项目着重于特定类型的视网膜 神经节电池，该细胞发出了运动方向，称为方向选择性神经节细胞（DSGC）。录音 来自小鼠和兔子中的视野隔离视网膜制剂的DSGC将用于表征 这些细胞的电和形态特性。神经电路的现实计算模型将 根据此信息生成。将使用模型系统对真实响应的概括 测试我们对潜在神经回路的理解。该研究包括三个部分。目标1 检查Starburst Amacrine细胞（SBAC）的功能，这是一种方向来源的中间神经元 DSGC的选择性抑制输入。这个目的检验了SBAC中几种机制的假设 树突产生并放大方向选择性抑制信号。 SBAC的计算机模型 电路将包括与相互关联的SBAC网络中的钠和钙通道 抑制。 AIM 2检验了围绕抑制作用的假设调节强度和空间和时间。 突触输入分辨率为DSGC。实验结果将用于扩展计算机 模型要考虑到整合较大信息整合信息的抑制性输入 DSGC周围视觉场景的区域。 AIM 3检查了尖峰输出的可靠性 DSGC，以及视觉输入中歧义和噪声的存在如何影响。获得的数据 将用于进一步开发计算机模型以模拟DSGC Spike响应。最终模型，基于 关于所有三个目标的生理结果 哺乳动物视网膜中定向信号的神经机制。如果成功，模型 应重现任何视觉刺激的现实尖峰输出。总体而言，拟议的研究将改善 我们对成人视网膜复杂电路的理解；获得的知识将为继续 努力开发治疗和视觉假体设备，以恢复各种眼睛的视力丧失 疾病。