Pacemakers of Cholinergic Wave Activity in the Developing Retina

视网膜发育中胆碱能波活动的起搏器

• 批准号: 10653330
• 负责人: Dao-Qi Zhang
• 金额: $ 42.9万
• 依托单位: OAKLAND UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10653330
• 关键词: Address; Biomedical Research; Blood Vessels; Brain; Calcium; Calcium Channel; Cells; Communities; Critical Thinking; Data; Detection; Development; Dyes; Exhibits; Eye; Fetus; Future; Generations; Goals; Human; Image; Immunohistochemistry; Injections; Interneurons; Knowledge; Label; Laboratories; Lead; Learning; Location; Maps; Mediating; Medicine; Molecular; Monitor; Morphology; Mus; Neurodevelopmental Disorder; Neurons; Pacemakers; Pharmacotherapy; Photons; Physiological; Premature Infant; Primates; Property; Public Health; Recurrence; Research; Research Personnel; Retina; Retinal Ganglion Cells; Reverse Transcriptase Polymerase Chain Reaction; Role; Students; Systems Development; Techniques; Testing; Transgenic Mice; United States; Vision; Visual; Visual Motion; Visual impairment; Work; angiogenesis; calcium indicator; career; cholinergic; experience; graduate student; nervous system disorder; neural; neural circuit; neuron development; novel; patch clamp; pharmacologic; prenatal; retinotopic; segregation; skills; starburst amacrine cell; tool; two photon microscopy; two-photon; undergraduate student; vision development; visual processing

PROJECT SUMMARY Before the emergence of vision, spontaneous retinal wave activity is essential for retinal layer-specific angiogenesis and dendritic maturation of retinal ganglion cells, as well as for the refinement of eye-specific segregations and retinotopic maps. A subpopulation of retinal amacrine interneurons, called starburst amacrine cells, initiate and propagate retinal waves through recurrent cholinergic connections called cholinergic retinal waves. However, the mechanisms underlying cholinergic wave initiation and propagation are poorly defined. Currently, the most urgent priority is to define how cholinergic waves are initiated to create a framework for understanding their downstream propagation. This project's objective is to identify a subset of starburst amacrine cells that serve as cholinergic wave pacemakers and the mechanisms by which pacemaker starburst amacrine cells generate these waves. Preliminary data from the PI's laboratory demonstrate that it is feasible to identify pacemaker starburst amacrine cells and the sufficiency of a single pacemaker starburst amacrine cell to initiate a wave. Wave generation requires activation of voltage-dependent calcium channels. These novel findings lead to the central hypothesis: single pacemaker starburst amacrine cells initiate waves by a calcium-dependent mechanism. To test this hypothesis, the team will determine the distribution and properties of cholinergic wave pacemakers (Aim 1), and identify the calcium-dependent mechanisms of cholinergic wave generation (Aim 2). The work on understanding the identity and features of pacemaker starburst amacrine cells and the ionic mechanisms of cholinergic retinal wave generation will advance knowledge of how retinal waves mediate vascular and neuronal development of the retina as well as eye-specific segregation and retinotopic map refinement in the visual centers of the brain.

项目摘要 在视觉出现之前，自发的视网膜波活动对于视网膜特异性是必不可少的 视网膜神经节细胞的血管生成和树突状成熟，以及眼睛特异性的细化 隔离和视网膜图。视网膜间氨基核元的亚群，称为Starburst amacrine 细胞通过称为胆碱能视网膜的复发性胆碱能连接引发和传播视网膜波 波浪。但是，胆碱能波的起始和传播的机制的定义很差。 目前，最紧迫的优先事项是定义如何发起胆碱能波以创建一个框架 了解他们的下游传播。该项目的目标是确定一部分Starburst Amacrine 用作胆碱能波起搏器的细胞以及起搏器starburst amacrine的机制 细胞产生这些波。 PI实验室的初步数据表明，可以识别 起搏器starburst amacrine细胞和单个起搏器starburst amacrine细胞的足够启动 波浪。波产生需要激活电压依赖性钙通道。这些新颖的发现导致 中央假设：单个起搏器Starburst Amacrine细胞通过钙依赖性启动波 机制。为了检验这一假设，团队将确定胆碱能波的分布和特性 起搏器（AIM 1），并确定胆碱能波产生的钙依赖性机制（AIM 2）。 了解起搏器starburst amacrine细胞和离子的身份和特征的工作 胆碱能视网膜波产生的机制将提高视网膜波如何介导的知识 视网膜的血管和神经元发育以及特异性的隔离和视网膜图 大脑视觉中心的细化。