Retinal Circuitry for Robust Direction Selectivity

视网膜电路具有强大的方向选择性

• 批准号: 8775226
• 负责人: Robert G Smith
• 金额: $ 38.47万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 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 2016-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8775226
• 关键词: Accounting; Adult; Biophysical Process; Blindness; Brain; Cells; Chloride Ion; Chlorides; Code; Complex; Computer Simulation; Contracts; Coupled; Dendrites; Development; Elements; Environment; Eye; Eye diseases; Feedback; Goals; Human; Image; In Vitro; Knowledge; Life; Light; Lighting; Modeling; Morphology; Motion; Neurons; Noise; Oryctolagus cuniculus; Output; Physiological; Potassium Channel; Process; Property; Prosthesis; Publications; Research; Research Project Grants; Retina; Retinal; Retinal Ganglion Cells; Signal Transduction; Stimulus; Synapses; Testing; Training; Trees; Visual; Visual system structure; Work; area striata; base; biophysical model; cell type; coping; ganglion cell; improved; light intensity; neuromechanism; neurophysiology; novel therapeutics; postsynaptic; presynaptic; prevent; response; starburst amacrine cell; transmission process; voltage; voltage gated channel

DESCRIPTION (provided by applicant): This project proposes to study mechanisms of synaptic processing within specific ganglion cell types in the mammalian retina, both by direct neurophysiological recording and through the use of realistic computer models. Our visual system functions under a wide range of light conditions from night to day, and the retina adapts to prevent saturation, so that the output is largely invariant to changes in the illumination level. The synaptic mechanisms that accomplish adaptation and signal transmission introduce noise, which, coupled with the limited dynamic range of neurons, reduces the fidelity of the visual signal. To cope with this problem, the retina segments the visual world using different types of ganglion cells that each code specific visual features with high fidelity. This project focuses on a specific type of retinal ganglion cell that signals directional motion, called the direction-selective ganglion cell (DSGC). Using a live in-vitro isolated rabbit retina, we will record responses of neurons to light stimuli, and construct computational models of the responses to determine the biophysical mechanisms present. The study comprises three sections. Aim 1 examines the function of the starburst amacrine cell (SBAC), essential for generating the direction selective signal for the DSGC. This aim tests several hypotheses relating to specific biophysical mechanisms intrinsic to the cell, such as voltage-gated channels, that generate its directional output. A realistic computer model of the SBAC will help to determine which mechanisms are present. Aim 2 tests the hypothesis that inhibition between adjacent cells within the network of SBACs is crucial for amplifying directional signals. The experimental results will be used to develop and test a computational model, derived from the results of Aim 1 that contains several SBACs with their network interactions. Aim 3 examines noise and precision in the spiking output of the direction-selective ganglion cell, and will account for its spiking properties using a computational model based on physiological results from all three Aims. The final model will represent a detailed and essentially complete representation of directional signaling in the mammalian retina. 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.

描述（由申请人提供）：该项目提议通过直接的神经生理记录以及通过使用现实的计算机模型来研究哺乳动物视网膜特定神经节细胞类型中突触处理的机制。我们的视觉系统从夜间到夜间在广泛的光线条件下发挥作用，视网膜适应以防止饱和度，因此输出在很大程度上是照明水平变化的不变性。完成适应和信号传递的突触机制会引入噪声，再加上神经元的动态范围有限，可降低视觉信号的忠诚度。为了应对这个问题，视网膜使用不同类型的神经节单元将视觉世界段片段段，每个神经节细胞都以高忠诚为特定的视觉特征。该项目着重于特定类型的视网膜神经节细胞，该细胞标志着方向运动，称为方向选择性神经节细胞（DSGC）。使用活体内隔离的兔视网膜，我们将记录神经元对光刺激的反应，并构建反应的计算模型，以确定存在的生物物理机制。该研究包括三个部分。 AIM 1检查了Starburst Amacrine细胞（SBAC）的功能，对于生成DSGC的方向选择性信号至关重要。该目标检验了与细胞固有的特定生物物理机制有关的几种假设，例如电压门控通道，它们会产生其方向输出。 SBAC的现实计算机模型将有助于确定存在哪些机制。 AIM 2检验了以下假设：SBAC网络中相邻细胞之间的抑制作用对于放大方向信号至关重要。实验结果将用于开发和测试一个计算模型，该计算模型源自AIM 1的结果，该结果包含与其网络相互作用的几个SBAC。 AIM 3检查了方向选择性神经节细胞的尖峰输出中的噪声和精度，并将使用基于所有三个目标的生理结果的计算模型来考虑其峰值特性。最终模型将代表哺乳动物视网膜中定向信号传导的详细且完全完整的表示。总体而言，拟议的研究将提高我们对成人视网膜复杂电路的理解。获得的知识将为开发疗法和视觉假体设备的持续努力提供信息，这些设备可恢复各种眼部疾病的视力丧失。