Exploring plasticity of the adult visual system using viral gene delivery

描述(由申请者提供)：本次拨款申请中提出的工作的长期目标是通过增加新的感觉输入来研究成年哺乳动物视觉系统的神经可塑性。增强而不是削弱感觉输入的实验为回答有关成人视觉系统可塑性的基本问题提供了一条新的研究途径，并对基因治疗和视网膜假体的合理设计具有重要意义。我们选择红绿色觉作为一个模型系统，在这个系统中，可以使用视网膜电信号在视网膜水平上定量监测功能获得，并通过色觉行为测试在视觉皮质水平上进行定量监测。作为实现长期目标的第一步，我们提出两个具体目标。 具体目的1.通过病毒介导法将感光基因导入成年二色松鼠猴的视网膜，确定加入第三种类型的视锥细胞能否扩大其感觉能力，并将颜色视觉行为从二色改变为三色。 具体目的2.通过病毒介导的基因传递到沙土鼠视网膜，确定在UV视锥的一个子集中表达长波敏感色素基因是否可以扩展沙土鼠的颜色视觉能力，包括在光谱的红绿区域进行颜色辨别。

DESCRIPTION (provided by applicant): The long-term goals of the work proposed in this grant application are to study neural plasticity of the adult mammalian visual system by adding new sensory input. Experiments that enhance rather than ablate sensory input offer a new avenue of research for answering fundamental questions about the plasticity of the adult visual system and have important implications for the rational design of gene therapy and retinal prostheses. We have chosen red-green color vision as a model system in which gain of function can be monitored quantitatively at the level of the retina using the electroretinogram and at the level of the visual cortex with behavioral tests of color vision. As a first step toward achieving our long term goals, we propose two specific aims. Specific Aim 1. To determine whether adding a third cone type via viral mediated delivery of a photopigment gene to the retina in a dichromatic adult squirrel monkey can expand his sensory capacity and change color vision behavior from dichromatic to trichromatic. Specific Aim 2. To determine whether expressing a long-wavelength sensitive pigment gene in a subset of UV cones via viral mediated gene delivery to the gerbil retina can expand the gerbil's color vision capacity to include making color discriminations in the red-green region of the spectrum.