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/关无长突细胞中，TH2-AC 被敲除。 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 我们发现 TH2-AC 内在兴奋性在缺乏的情况下增强。 我们认为 TPBG 调节 TH2-AC 兴奋性，TH2-AC 调节视网膜回路。 鉴于无长突细胞是最多样化的，但负责对比度和/或运动编码。 到目前为止，East 了解视网膜神经元，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）将完成这些独立目标。 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。