Neurotransmitter Mechanisms in the Mammalian Retina

哺乳动物视网膜中的神经递质机制

• 批准号: 9039609
• 负责人: STEPHEN C MASSEY
• 金额: $ 45.27万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-09-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9039609
• 关键词: Amacrine Cells; Antibodies; Brain region; Calcium-Sensing Receptors; Cartoons; Cells; Color; Cone; Confocal Microscopy; Connexins; Coupled; Coupling; Dark Adaptation; Dendrites; Dopamine; Electron Microscopy; Engineering; Gap Junctions; Glutamate Receptor; Goals; Health; Image; Individual; Knockout Mice; Knowledge; Label; Light; Maps; Meclofenamic Acid; Mediating; Modeling; Mus; N-Methyl-D-Aspartate Receptors; Natural regeneration; Neuronal Plasticity; Neurons; Neurotransmitters; Oryctolagus cuniculus; Output; Pathway interactions; Pattern; Photons; Photoreceptors; Physiological; Physiology; Play; Population; Presynaptic Terminals; Reporting; Research; Retina; Retinal; Role; Signal Transduction; Slice; Structure; System; Techniques; Testing; Time; Tracer; Transgenic Organisms; Transplantation; Variant; Vertebrate Photoreceptors; Vision; Visual; Work; cell type; light intensity; neurobiotin; novel; novel strategies; response; retinal rods

DESCRIPTION (provided by applicant): In many brain regions, electrical coupling, mediated primarily by Cx36 gap junctions, contributes to neuronal plasticity. In the retina, gap junctions are particularly abundant and they play a key role in the switch from rod to cone pathways. This is an important example of neuronal plasticity that makes the retina a useful system to study gap junction modulation. The mammalian retina detects light over an enormous range of intensities, approximately 12 log units. Furthermore, there are distinct pathways through the retina for both rod and cone signals, in part mediated by gap junction connections. The goal of this research is to test rod and cone connections and determine the physiological role of gap junctions in rod and cone pathways. Specific Aim1 is to map the connections of rods and cones to bipolar cells. By filling single rod bipolar cells in rabbit, we can determine their rod or cone contacts unambiguously. Most ON cone bipolar cells can be labeled via their coupling with AII amacrine cells, providing a novel way to view ON bipolar connections with rods and cones. Controversial results from mouse retina suggested two types of rod bipolar cell (RBC), one of which receives cone input. We will test this hypothesis by recording from mouse bipolar cells and correlating physiology with confocal analysis of rod/cone contacts. In Specific Aim 2, the working hypothesis is that there are 3 kinds of photoreceptor coupling, cone/cone, rod/cone and rod/rod, all using Cx36. Taking a transgenic approach, using rod-specific and cone-specific Cx36 KO mice, we will correlate single photon responses in rods with Neurobiotin coupling patterns and the distribution of Cx36 gap junctions. This will identify the rod connexin and establish the physiological role of Cx36 in rod/rod and rod/cone coupling. Specific Aim 3: AII amacrine cells are a well-known example of well-coupled network. Plasticity in this network is responsible for major changes in retinal circuitry underlying the switch from rod to cone pathways. There is circumstantial evidence that dopamine modulates AII coupling but no direct physiological evidence. We have developed a novel technique in mouse retinal slices to estimate AII network coupling. We have validated this approach using gap junction antagonists and Cx36 KO mice. Here, we report for the first time that dopamine modulates electrical coupling in the AII network. The mammalian retina is a self-optimizing network of around seventy different neuronal cell types. The retina detects light but in addition it is continually adjusting to the intensity and pattern of the visual scene to provide the best output. It is important to understand the structure and function of retinal circuits. Such knowledge will be required to test if transplanted or regenerated cells form appropriate functional connections.

描述（由申请人提供）：在许多大脑区域，电气耦合，主要由CX36间隙连接介导，促进了神经元可塑性。在视网膜中，间隙连接特别丰富，它们在从杆到圆锥形路径的转换中起着关键作用。这是神经元可塑性的重要例子，它使视网膜成为研究间隙连接调制的有用系统。哺乳动物的视网膜检测到大量强度（约12个原木单元）上的光。此外，对于杆和锥体信号，通过视网膜有不同的途径，部分是由间隙连接连接介导的。这项研究的目的是测试杆和锥形连接，并确定间隙连接在杆和锥途径中的生理作用。 特定的目标是绘制杆和锥形与双极细胞的连接。通过填充兔子中的单杆双极细胞，我们可以确定它们的棒或锥 明确接触。锥双极细胞上的大多数都可以通过与AII无4acarine细胞的耦合标记，从而提供了一种新颖的方式来查看与杆和锥形的双极连接。小鼠视网膜的有争议的结果表明，两种类型的杆双极细胞（RBC），其中一种接收锥输入。我们将通过记录小鼠双极细胞并将生理学与棒/锥接触的共焦分析相关的生理学来检验这一假设。 在特定的目标2中，工作假设是使用CX36有3种类型的光感受器耦合，锥/锥，杆/锥和杆/杆。采用转基因方法，使用杆特异性和锥体特异性CX36 KO小鼠，我们将与神经益素偶联模式的棒中的单个光子响应以及CX36间隙连接的分布相关联。这将识别杆连接素，并确定CX36在杆/杆和杆/锥耦合中的生理作用。 特定的目标3：AII amacrine细胞是耦合良好的网络的众所周知的例子。该网络中的可塑性负责从杆到锥途径开关开关的视网膜电路的重大变化。有间接的证据表明多巴胺会调节AII耦合，但没有直接的生理证据。我们已经在小鼠视网膜切片中开发了一种新型技术来估计AII网络耦合。我们已经使用GAP连接拮抗剂和CX36 KO小鼠验证了这种方法。在这里，我们首次报告多巴胺调节AII网络中的电耦合。 哺乳动物视网膜是大约70种不同神经元细胞类型的自优化网络。视网膜检测到光，但此外，它正在不断调整视觉场景的强度和模式，以提供最佳的输出。了解视网膜电路的结构和功能很重要。需要进行此类知识才能测试是否形成适当的功能连接的移植或再生细胞。