Retinal Circuitry for Robust Direction Selectivity

描述(申请人提供)：该项目建议通过直接神经生理学记录和使用现实的计算机模型来研究哺乳动物视网膜中特定神经节细胞类型内的突触处理机制。我们的视觉系统在从夜间到白天的各种光线条件下工作，视网膜适应以防止饱和，因此输出在很大程度上不随照明水平的变化而变化。完成适应和信号传递的突触机制引入了噪声，再加上神经元有限的动态范围，降低了视觉信号的保真度。为了解决这个问题，视网膜使用不同类型的神经节细胞来分割视觉世界，每个神经节细胞都高保真地编码特定的视觉特征。这个项目专注于一种特定类型的视网膜神经节细胞，它发出定向运动的信号，称为方向选择性神经节细胞(DSGC)。利用体外分离的活体兔视网膜，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。这项研究包括三个部分。目的1研究星暴无长突细胞(SBAC)的功能，该细胞是产生方向选择信号所必需的。这一目标测试了几个与细胞固有的特定生物物理机制有关的假设，例如产生其定向输出的电压门控通道。SBAC的真实计算机模型将有助于确定存在哪些机制。目的2验证SBAC网络中相邻细胞之间的抑制对放大定向信号至关重要的假设。实验结果将被用来开发和测试一个计算模型，该模型来自目标1的结果，该模型包含几个具有网络交互作用的SBAC。AIM 3检查了方向选择性神经节细胞刺激性输出中的噪声和精确度，并将使用基于所有三个AIMS的生理结果的计算模型来解释其刺激性。最终的模型将代表哺乳动物视网膜中定向信号的详细和基本完整的表示。总体而言，拟议的研究将提高我们对成人视网膜复杂回路的理解；所获得的知识将有助于继续努力开发治疗方法和视觉假体设备，以恢复一系列眼病造成的视力损失。 与公共健康相关：这项研究项目的总体目标是了解眼睛中特定的神经细胞，即视网膜神经节细胞，如何检测我们环境中的运动，并将信息传递给大脑。提高我们对健康眼睛的理解将为人类眼病的新治疗方法的持续发展提供信息和促进。

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. PUBLIC HEALTH RELEVANCE: The overall goal of this research project is to understand how specific nerve cells in the eye, the retinal ganglion cells, detect motion in our environment and relay that information to the brain. Improving our understanding of the healthy eye will inform and facilitate the continued development of novel therapeutic treatments for human eye disease.