FUNCTIONAL ORGANIZATION OF VISUAL SYSTEMS

视觉系统的功能组织

• 批准号: 2444245
• 负责人: JOHN E DOWLING
• 金额: $ 23.24万
• 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 1999-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2444245
• 关键词: GABA receptor; Osteichthyes; Xenopus oocyte; amacrine cells; dopamine; electrophysiology; gamma aminobutyrate; glutamates; horizontal cell; membrane channels; neurophysiology; retina; retinal bipolar neuron; retinal ganglion; synapses; tissue /cell culture; ultraviolet radiation; visual photoreceptor; voltage /patch clamp; zebrafish

This project is attempting to learn more about retinal synaptic mechanisms. In particular, we are seeking to discover what substances are used at specific synaptic junctions and what effects these substances have on retinal cells. It is now generally believed that two basic types of substances are released at brain synapses; neurotransmitters which initiate fast excitatory and inhibitory responses in neural cells, and neuromodulators which mediate slow, long lasting events in nerve cells. The next five years of this project will focus on the action of, and interaction between, glutamate, a classic neurotransmitter,and dopamine, a classic neuromodulator, on bipolar, amacrine and ganglion cells of the fish (white perch retina). We also will study the pharmacology and molecular biology of a newly identified GABA receptor/channel, the GABA-c receptor, from white perch or hybrid bass retinas. Finally, recordings will be made from cone photoreceptors of zebrafish that absorb maximally in the ultraviolet region of the spectrum. Specific projects planned for the next five years include: 1) A study of amino acid-gated channels in retinal bipolar, amacrine and ganglion cells and their modulation by dopamine and other neuroactive substances. This project is focusing initially on the glutamate-mediated responses of bipolar cells. Bipolar cells in retinal slices are voltage- clamped with patch electrodes and the glutamate responses characterized. 2) A study of the pharmacological and molecular biological properties of GABA-c receptors in retinal horizontal cells and in Xenopus oocytes. This project will examine the conformation of GABA that best activates these novel receptors. This part of the project will employ conformationally- restricted GABA analogues and isolated rod (H4) horizontal cells from the white perch or hybrid bass retinas. Other studies will involve expressing in Xenopus oocytes the gene(s) encoding the subunits that make up these novel receptors. 3) An investigation of the response properties of ultraviolet-sensitive photoreceptors. This project will explore the response properties of UV- sensitive cones isolated from the zebrafish. Suction electrodes will record the currents generated by these photoreceptors.

该项目试图更多地了解视网膜突触 机制。 特别是，我们正在寻求发现什么物质 在特定突触连接处使用以及这些物质有什么作用 在视网膜细胞上。现在普遍认为有两种基本类型 大脑突触释放物质；神经递质其中 启动神经细胞的快速兴奋和抑制反应，并且 神经调节剂介导神经细胞中缓慢而持久的事件。 该项目的未来五年将重点关注以下行动： 谷氨酸（一种经典的神经递质）和多巴胺之间的相互作用， 一种经典的神经调节剂，作用于双极细胞、无长突细胞和神经节细胞 鱼（白鲈视网膜）。我们还将研究药理学和 新发现的 GABA 受体/通道（GABA-c）的分子生物学 受体，来自白鲈或混合鲈鱼的视网膜。 最后是录音 将由斑马鱼的锥体光感受器制成，吸收最大 在光谱的紫外区域。 未来五年规划的具体项目包括： 1) 视网膜双极、无长突和视网膜氨基酸门控通道的研究 神经节细胞及其多巴胺和其他神经活性物质的调节 物质。 该项目最初侧重于谷氨酸介导的 双极细胞的反应。 视网膜切片中的双极细胞是电压- 用贴片电极夹紧并表征谷氨酸反应。 2) 药理和分子生物学特性的研究 视网膜水平细胞和非洲爪蟾卵母细胞中的 GABA-c 受体。 这 项目将检查最能激活这些的 GABA 构象 新的受体。该项目的这一部分将采用构象- 限制性 GABA 类似物和分离杆 (H4) 水平细胞 白色鲈鱼或混合鲈鱼视网膜。其他研究将涉及表达 在非洲爪蟾卵母细胞中，编码组成这些亚基的基因 新的受体。 3) 紫外敏感材料的响应特性研究 光感受器。该项目将探索紫外线的响应特性 从斑马鱼中分离出敏感视锥细胞。抽吸电极将 记录这些感光器产生的电流。