ON and OFF visual signaling in the retinal interneurons

视网膜中间神经元中的ON和OFF视觉信号

• 批准号: 10610970
• 负责人: Tomomi Ichinose
• 金额: $ 36.93万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10610970
• 关键词: Affect; Amacrine Cells; Biological; Calcium; Cells; Code; Darkness; Detection; Excitatory Postsynaptic Potentials; Exhibits; Functional disorder; Goals; Image; Inner Plexiform Layer; Interneurons; Interruption; Light; Light Adaptations; Mediating; Molecular; Morphology; Motion; Mus; Neurons; Outcome; Output; Pathway interactions; Photoreceptors; Physiological; Play; Preparation; Retina; Role; Shapes; Signal Pathway; Signal Transduction; Stimulus; System; Technology; Testing; Tissues; Vertebrate Photoreceptors; Vision; Visual; Visual impairment; Whole-Cell Recordings; cell type; ganglion cell; horizontal cell; patch clamp; pharmacologic; response; retinal neuron; signal processing; starburst amacrine cell; tool

Abstract Retinal neurons utilize multiple antagonistic mechanisms to shape visual signal processing, such as ON and OFF signaling, antagonistic center-surround, rod- and cone-signaling, and transient and sustained signaling. Among those signaling mechanisms, ON vs. OFF signaling is coded to morphologically distinct groups of retinal neurons, bipolar, amacrine, and ganglion cells. Retinal neurons that ramify in the inner region of the inner plexiform layer (IPL) respond to the onset of a light stimulus, called ON cells. In contrast, OFF cells ramify in the outer region of the IPL and respond to the offset of a light stimulus. Since being discovered several decades ago, there appeared to be no exceptions to this morpho-physiological rule for ON and OFF signaling. However, recently, some exceptions have been revealed. We found that ON and OFF signaling switches in starburst amacrine cells and bipolar cells. We also found that light adaptation plays a crucial role in the ON and OFF sign switch. In the mesopic light condition, both rods and cones are active, generating a complicated interaction. However, light-evoked responses in retinal interneurons, including bipolar and amacrine cells, have not been systematically investigated over a wide range of ambient light levels. In our proposed studies, we will test the hypothesis that the rod-cone interaction in the mesopic condition converts the ON and OFF signs of light responses in retinal bipolar cells and amacrine cells. The long-term goal of the proposed study is to examine how the ON and OFF sign switch occurs in the interneuron and how this plays a role in shaping spikes in ganglion cells. We will use wholemount retinal preparations to conduct a patch clamp study of bipolar and amacrine cells to determine the visual signal signs in response to various light stimuli. Especially, we will assess the light-evoked excitatory postsynaptic potentials (L-EPSPs) over a wide range of background light conditions. We will also examine the L-EPSPs at the mesopic condition after the tissue is adapted to scotopic or photopic conditions (Aim 1). Also, we will determine how retinal antagonistic signaling systems shape the ON and OFF signs. We will test potential underlying mechanisms, including the rod-cone signaling interaction, the dopaminergic system, the antagonistic surround by inhibitory amacrine cells, and the ON-OFF signaling pathway interaction (Aim 2). Then, we will examine the outcome of the switch by conducting the Calcium imaging from the starburst amacrine cells (Aim 3). Understanding the mesopic vision is essential because both rod and cone dysfunction cause reduced vision in the mesopic vision.

摘要 视网膜神经元利用多种拮抗机制来塑造视觉信号处理，例如ON和 OFF信号传导、拮抗性中心-环绕、视杆和视锥信号传导以及瞬时和持续信号传导。 在这些信号传导机制中，ON与OFF信号传导被编码为形态上不同的组， 视网膜神经元、双极、无长突和神经节细胞。视网膜神经元在视网膜的内部区域分支， 内丛状层（IPL）对光刺激的开始作出反应，称为ON细胞。相反，OFF细胞 在IPL的外部区域分叉并对光刺激的偏移作出响应。自从被发现 几十年前，ON和OFF的形态生理学规律似乎没有例外 发信号。然而，最近却出现了一些例外。我们发现ON和OFF信号 星状无长突细胞和双极细胞中的开关。我们还发现，光适应在 ON和OFF标志开关。在中间光条件下，视杆细胞和视锥细胞都是活跃的，产生一种视觉刺激。 复杂的互动。然而，视网膜中间神经元的光诱发反应，包括双极和 无长突细胞，还没有在广泛的环境光水平范围内进行系统的研究。在我们 提出的研究，我们将测试假设，即杆锥相互作用在介视条件下转换 视网膜双极细胞和无长突细胞光反应的ON和OFF信号。的长期目标 拟议的研究是研究如何在中间神经元中发生ON和OFF符号转换，以及这如何发挥作用。 在神经节细胞中形成尖峰的作用。我们将使用全视网膜标本进行膜片钳检查 双极细胞和无长突细胞的研究，以确定响应各种光刺激的视觉信号符号。 特别是，我们将评估光诱发兴奋性突触后电位（L-EPSP）在广泛的范围内， 背景光条件。我们还将在组织被分离后在中间视觉条件下检查L-EPSP。 适应暗视或明视条件（目标1）。此外，我们将确定视网膜拮抗信号如何 系统塑造了ON和OFF标志。我们将测试潜在的潜在机制，包括杆锥 信号相互作用，多巴胺能系统，抑制性无长突细胞的拮抗性包围，以及 ON-OFF信号通路相互作用（Aim 2）。然后，我们将通过进行以下操作来检查切换的结果： 星爆型无长突细胞的钙离子显像（Aim 3）。了解中间视觉是至关重要的 因为视杆细胞和视锥细胞功能障碍都导致中间视觉的视力降低。