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

基本信息

批准号：
10503482
负责人：
Ching-Kang Jason Chen
金额：
$ 4.64万
依托单位：
BAYLOR COLLEGE OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-01 至 2023-03-01
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10503482
关键词：
Ablation Adult Affect Amacrine Cells Behavioral Brain Calcium Caliber Catalogs Cells Closure by clamp Contrast Sensitivity Data Detection 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 Pharmacology 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 mouse genetics object motion postsynaptic presynaptic response retinal neuron success trophoblast tumor visual information voltage

Ablation Adult Affect Amacrine Cells Behavioral Brain Calcium Caliber Catalogs Cells Closure by clamp Contrast Sensitivity Data Detection 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 Pharmacology 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 mouse genetics object motion postsynaptic presynaptic response retinal neuron success trophoblast tumor visual information voltage

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项目摘要

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）在成人视网膜中限制表达在杆双极细胞和宽场Gabaergic中，无链氨酸细胞，Th2-Ac。淘汰TPBG 小鼠中的基因不会改变Scotopic或Photopic ERG反应增强，表明TPBG通过TH2-AC参与剩余信息处理身份不明的机制。我们发现，在没有的情况下，Th2-Ac的内在激动 TPBG。我们假设TPBG调节Th2-AC兴奋性，并且Th2-AC调节残留电路负责对比和/或运动编码。鉴于无聚细胞是最潜水员，但 East了解到目前为止的视网膜神经元，在Th2-AC中研究TPBG为难得的机会提供了难得的机会了解在哺乳动物视网膜中的宽场无链氨氨酸细胞的作用。我们将使用鼠标遗传学 1）使用Datirescre驱动器鼠标线操纵Th2-Ac到了解增强的光波对比灵敏度表型的分子和细胞基础 TPBG敲除动物（AIM-1）和2）从遗传和/或实际上从视网膜上燃烧Th2-Ac进行研究 OKR和细胞在行为层面上如何影响视网膜对比度和运动编码 TH2-AC的八个突触后RGC合作伙伴（AIM-2）中的水平。这些独立目标的完成将可以更好地理解宽阔的无链酰胺细胞如何在哺乳动物视网膜中起作用。