Retinal Circuitry for Robust Direction Selectivity

描述（由申请人提供）：本项目拟通过直接神经生理学记录和使用逼真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晚到白天的各种光照条件下工作，视网膜会进行适应以防止饱和，因此输出在很大程度上不随照明水平的变化而变化。完成适应和信号传输的突触机制引入了噪声，加上神经元有限的动态范围，降低了视觉信号的保真度。为了科普这个问题，视网膜使用不同类型的神经节细胞分割视觉世界，每个神经节细胞都以高保真度编码特定的视觉特征。该项目的重点是一种特定类型的视网膜神经节细胞，信号定向运动，称为方向选择性神经节细胞（DSGC）。使用活的离体兔视网膜，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。研究报告包括三个部分。目的1研究星爆无长突细胞（SBAC）的功能，它是产生DSGC方向选择信号的关键。这一目的测试了几个假设有关的具体生物物理机制的内在细胞，如电压门控通道，产生其定向输出。SBAC的现实计算机模型将有助于确定存在哪些机制。目的2检验SBAC网络内相邻细胞之间的抑制对于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，来自目标1的结果，其中包含几个SBAC与他们的网络相互作用。目标3检查方向选择性神经节细胞的尖峰输出的噪声和精度，并将使用基于所有三个目标的生理结果的计算模型来解释其尖峰特性。最终的模型将代表一个详细的和基本上完整的表示在哺乳动物视网膜的方向信号。总的来说，拟议中的研究将提高我们对成人视网膜复杂电路的理解;所获得的知识将为继续努力开发治疗和视觉假体设备提供信息，以恢复一系列眼科疾病造成的视力丧失。 公共卫生相关性：该研究项目的总体目标是了解眼睛中的特定神经细胞，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型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.