The function of wide-field amacrine cells in mammalian retina

哺乳动物视网膜广域无长突细胞的功能

• 批准号: 10915015
• 负责人: Ching-Kang Jason Chen
• 金额: $ 38.75万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2027-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10915015
• 关键词: Ablation; Adult; Affect; Amacrine Cells; Behavioral; Brain; Calcium; Catalogs; Cells; Closure by clamp; Contrast Sensitivity; Data; Detection; Diameter; Disease; Electrophysiology (science); Embryonic Development; Frequencies; Future; Genes; Glutamates; Glycoproteins; Human; Knock-out; Knowledge; Label; Light; Measures; Membrane; Modeling; Molecular; Morphology; Motion; Mus; Museums; Names; Neurons; Output; Pattern; Phenotype; Photophobia; Photoreceptors; Physiology; Presynaptic Terminals; Property; Proteins; Reflex action; Research; Retina; Retinal Ganglion Cells; Rod; Role; Source; Stimulus; Stratification; Synapses; Synaptic Transmission; Testing; Therapeutic; Time; Viral; Vision; Visual; Visual Acuity; Work; cell type; connexin 36; contrast enhanced; extracellular; horizontal cell; information processing; interdisciplinary approach; knockout animal; meter; mouse genetics; object motion; pharmacologic; postsynaptic; presynaptic; response; retinal neuron; success; transmission process; trophoblast; tumor; visual information; voltage

The trophoblast glycoprotein (TPBG, aka oncofaeto protein, 5T4) is restrictively expressed in adult retina in rod bipolar cell and the wide-field GABAergic ON/OFF amacrine cell, TH2-AC. Knocking out the Tpbg gene in mice does not alter scotopic or photopic ERG responses but photopic contrast sensitivity was enhanced, indicating that TPBG in TH2-AC participates in retinal information processing through unidentified mechanism. We have found that TH2-AC intrinsic excitability is enhanced in the absence of TPBG. We hypothesize that TPBG regulates TH2-AC excitability and that TH2-AC regulates retinal circuits responsible for contrast and/or motion encoding. Given that amacrine cell is the most diverse but lthe east understood retinal neuron thus far, studying TPBG in TH2-AC provides a rare opportunity to understand how wide-field amacrine cell works in the mammalian retina. We will use mouse genetics and electrophysiological approaches to 1) Use the DATIRESCre driver mouse line to manipulate TH2-AC to understand the molecular and cellular basis of the enhanced photopic contrast sensitivity phenotype of the Tpbg knockout animals (Aim-1) and 2) Genetically and/or virally ablate TH2-AC from retina to study how retinal contrast and motion encoding are affected at the behavioral level by OKR and at the cellular level in TH2-AC’s eight postsynaptic RGC partners (Aim-2). Completion of these independent aims will lead to a better understanding on how a wide-field amacrine cell works in a mammalian retina.

滋养层糖蛋白（TPBG，aka oncofaeto蛋白，5 T4）在成人视网膜中限制性表达 在视杆双极细胞和宽视野GABA能ON/OFF无长突细胞中，TH 2-AC。淘汰TPBG 小鼠的基因并不改变暗适应或明视ERG反应，但明视对比敏感度 增强，表明TH 2-AC中的TPBG通过以下方式参与视网膜信息处理 不明机制我们已经发现，TH 2-AC的内在兴奋性在缺乏 TPBG。我们假设TPBG调节TH 2-AC兴奋性，TH 2-AC调节视网膜回路 负责对比度和/或运动编码。鉴于无长突细胞是最多样化的， 迄今为止，我们已经了解了视网膜神经元，研究TH 2-AC中的TPBG提供了难得的机会， 了解宽视野无长突细胞如何在哺乳动物视网膜中工作。我们将使用老鼠遗传学 和电生理学方法来1）使用DATIRESCre驱动器鼠标线来操纵TH 2-AC， 了解增强明视对比敏感度表型的分子和细胞基础， Tpbg敲除动物（Aim-1）和2）从视网膜遗传和/或病毒清除TH 2-AC以研究 视网膜对比度和运动编码如何在行为水平上受到OKR的影响，以及在细胞水平上受到OKR的影响。 TH 2-AC的八个突触后RGC伙伴（Aim-2）中的水平。这些独立目标的实现将 从而更好地了解宽视野无长突细胞在哺乳动物视网膜中的工作方式。