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: 10863459
• 负责人: Ching-Kang Jason Chen
• 金额: $ 35.36万
• 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/10863459
• 关键词: function; wide; field; amacrine; cells

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，又名致癌蛋白，5T4）在成人视网膜中限制性表达 在视杆双极细胞和宽场 GABA 能开/关无长突细胞 TH2-AC 中。淘汰 Tpbg 小鼠基因不会改变暗视或明视 ERG 反应，但明视对比敏感度 增强，表明 TH2-AC 中的 TPBG 通过 机制不明。我们发现 TH2-AC 内在兴奋性在缺乏 TPBG。我们假设 TPBG 调节 TH2-AC 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化的，但 到目前为止，East 了解了视网膜神经元，研究 TH2-AC 中的 TPBG 提供了一个难得的机会 了解广域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 和电生理学方法 1) 使用 DATIRESCre 驱动鼠标线操纵 TH2-AC 了解增强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) 通过基因和/或病毒从视网膜消除 TH2-AC 以进行研究 OKR 在行为层面和细胞层面如何影响视网膜对比度和运动编码 TH2-AC 的八个突触后 RGC 伙伴的水平 (Aim-2)。完成这些独立目标将 有助于更好地了解广域无长突细胞在哺乳动物视网膜中的工作原理。