FUNCTIONAL ORGANIZATION OF VISUAL SYSTEM

视觉系统的功能组织

• 批准号: 6384262
• 负责人: JOHN E DOWLING
• 金额: $ 32.6万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1979
• 资助国家: 美国
• 起止时间: 1979-06-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6384262
• 关键词: GABA receptor; Xenopus oocyte; amacrine cells; dopamine; electrophysiology; electroretinography; gamma aminobutyrate; glutamates; horizontal cell; membrane channels; neurophysiology; retina; retinal bipolar neuron; retinal ganglion; rod cell; synapses; tissue /cell culture; visual photoreceptor; visual phototransduction; voltage /patch clamp; zebrafish

For the next five years of this project, we shall focus on experiments designed to elucidate the role of dopamine in the inner retina. In particular, we shall carry out experiments designed to uncover to role of dopamine in mediating rod signal transmission through the inner plexiform layer of the zebrafish. We shall also develop more sophisticated electrophysiological tests, based on electroretinographic (ERG) recordings, to analyze zebrafish retinal mutations. With behavioral tests, we have identified both recessive and dominant mutations that affect retinal function in zebrafish. A number of the mutations resemble inherited retinal diseases in man including dominantly- inherited retinitis pigmentosa (our nba mutant) protanopia (our pob mutant) and congenital stationary night blindness (our noa mutant). Further, electrophysiological testing of these mutants will help identify where in the retina a specific defect resides and more about the nature of the defect. Specific sub-projects planned for the next five years include: 1) An analysis of ganglion cell responses in normal zebrafish and zebrafish deprived of dopamine by the intraocular injection of 6- hydroxydopamine. Ganglion cells will be patch-clamped and synaptic currents evoked in the cells by puffs of K+ applied in the inner plexiform layer. 2) The electroretinogram (ERG) of the zebrafish will be dissected pharmacologically by drugs that selectively block transmission from photoreceptor cells to all second-order cells, transmission from rod photoreceptor cells to ON-bipolar cells, and transmission from rod and cone photoreceptor cells to OFF-bipolar cells. As part of this sub- project, the effects of these pharmacological manipulations on the visual performance of zebrafish will be tested behaviorally. 3) The ERG responses of selected zebrafish mutants will be further studied using the pharmacological manipulations described in (2) above. In particular, the effects of the mutations on photoreceptor (ERG a-wave) function will be examined.

在该项目的未来五年中，我们将重点关注旨在阐明多巴胺在视网膜内层中的作用的实验。 特别是，我们将进行旨在揭示多巴胺在介导通过斑马鱼内丛状层的杆信号传输中的作用的实验。我们还将开发基于视网膜电图（ERG）记录的更复杂的电生理学测试，以分析斑马鱼视网膜突变。 通过行为测试，我们发现了影响斑马鱼视网膜功能的隐性和显性突变。 许多突变类似于人类遗传性视网膜疾病，包括显性遗传性色素性视网膜炎（我们的 nba 突变体）、红色盲（我们的 pob 突变体）和先天性静止性夜盲症（我们的 noa 突变体）。 此外，对这些突变体的电生理学测试将有助于确定视网膜中特定缺陷所在的位置，并更多地了解缺陷的性质。 未来五年计划的具体子项目包括： 1）分析正常斑马鱼和通过眼内注射6-羟基多巴胺剥夺多巴胺的斑马鱼的神经节细胞反应。 神经节细胞将被膜片钳固定，并通过施加在内丛状层的 K+ 气流在细胞中诱发突触电流。 2）斑马鱼的视网膜电图（ERG）将通过药物进行药理学解剖，药物选择性地阻断从感光细胞到所有二级细胞的传输，从视杆细胞到ON-双极细胞的传输，以及从视杆细胞和视锥细胞到ON-双极细胞的传输。 OFF-双极细胞。 作为该子项目的一部分，将通过行为测试这些药理操作对斑马鱼视觉表现的影响。 3）将使用上面（2）中描述的药理学操作进一步研究所选斑马鱼突变体的ERG反应。 特别是，将检查突变对光感受器（ERG a 波）功能的影响。