Development of Retinal Receptive Fields

描述(申请人提供)：视觉神经元的一个重要特性是它们的感受野大小。这项拟议研究的一个长期目标是了解控制视网膜感受区生长的发育机制。我们最近证实，一种这样的机制依赖于扫描发育中的视网膜的自发活动波。该机制的四个假说涉及树突生长、感受野大小的优化、生长关键期和细胞间竞争。我们将在海龟的视网膜上测试这些假设，目的有四个： 1)我们将使用细胞内记录和树突染色来测试自发波是否通过扩大神经节细胞的树突树而导致神经节细胞感受野的生长。 2)海龟将在异常的光线环境中饲养，通过细胞外录音测试感受野是否增长到最佳大小，以平均噪音，同时不过度平滑图像。 3)钙离子荧光将帮助我们绘制波的图谱，并研究光是如何影响它们的。 4)我们将测试感受野的生长是否因为一个关键时期或细胞间的竞争而停止，通过在药物注射的Elvax视网膜植入过程中增加暗培养波的强度来测试。 这项研究有助于理解影响神经节细胞的几种发育病理。这些病理包括早产儿视网膜病变、视网膜变性、Refsum病、Leber遗传性视神经病变、视神经发育不良和视盘玻璃疣。除了了解病理，解开神经节细胞的可塑性可能有助于治疗它们的一种有前途的技术，即视网膜移植。在这样的移植过程中，细胞在发育过程中必须“自组织”。

DESCRIPTION (provided by applicant): An important property of visual neurons is their receptive-field size. One long-term goal of the proposed research is to understand the developmental mechanisms controlling the growth of retinal receptive fields. We recently established that one such mechanism depends on the spontaneous waves of activity that sweep developing retinas. Four hypotheses for this mechanism involve dendritic-tree growth, optimization of receptive-field size, critical period for growth, and inter-cell competition. We will test these hypotheses in the turtle retina with four aims: 1) We will use intracellular recordings and dendritic staining to test whether spontaneous waves cause receptive fields of ganglion cells to grow by enlarging their dendritic trees. 2) Turtles will be reared in abnormal light environments to test through extracellular recordings whether receptive fields grow to a size optimized to average out noise, while not over-smoothing the image. 3) Ca2+ fluorescence will help us map the waves and ask how light affects them. 4) We will test whether receptive-field growth stops because of a critical period or of an inter-cell competition by increasing the intensity of dark-reared waves though the retinal implantation of drug-laced Elvax. This study could help understand several developmental pathologies affecting ganglion cells. These pathologies include retinopathy of prematurity, retinal degeneration, refsum disease, Leber hereditary optic neuropathy, optic-nerve hypoplasia, and drusen of the optic disk. Besides understanding pathologies, unraveling ganglion-cell plasticity may help with a promising technique for one of their cures, namely, retinal transplantation. In such a transplantation, cells must "self-organize" as during development.