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.

滋养细胞糖蛋白(TPBG，又名oncofaeto蛋白，5T4)在成人视网膜中有限制性表达 在杆状双极细胞和广野GABA能开/关无长突细胞中，TH2-AC。击倒Tpbg 小鼠的基因不会改变暗视或明视的ERG反应，但明视对比敏感度 增强，提示TH2-AC中的TPBG通过 机制不明。我们发现，在没有TH2-AC的情况下，内源性兴奋性增强。 TPBG。我们假设TPBG调节TH2-AC的兴奋性，而TH2-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但最长的 EAST到目前为止了解了视网膜神经元，研究TH2-AC的TPBG提供了一个难得的机会 了解宽视野无长突细胞在哺乳动物视网膜中的工作原理。我们将使用小鼠遗传学 和电生理方法：1)使用DATIRESCre驱动鼠标线操纵TH2-AC以 了解增强型明视对比敏感度表型的分子和细胞基础 Tpbg基因敲除动物(AIM-1)和2)基因和/或病毒去除视网膜TH2-AC的研究 OKR如何在行为水平和细胞水平影响视网膜对比度和运动编码 TH2-AC的8个突触后RGC伙伴(AIM-2)中的水平。完成这些独立的目标将 让我们更好地理解宽视场无长突细胞在哺乳动物视网膜中的工作原理。