Amacrine Cell Function in the Retina

视网膜无长突细胞功能

基本信息

批准号：
7460146
负责人：
Stewart Allen Bloomfield
金额：
$ 58.23万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-03-01 至 2013-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7460146
关键词：
Acetylcholine Affect Amacrine Cells Applications Grants Architecture Area Axon Biological Assay Brain Cell physiology Cells Cellular Morphology Charcot-Marie-Tooth Disease Cholinergic Agents Circadian Rhythms Class Code Communication Computer Simulation Condition Conflict (Psychology)Connexins Coupled Coupling Data Data Collection Defect Dendrites Dopamine Dyes Economics Feedback GABA Receptor Gap Junctions Generations Goals Grant Human Individual Inner Nuclear Layer Intercellular Junctions Investigation Knock-out Knockout Mice Label Laboratories Light Light Adaptations Lighting Link Masks Mediating Methodology Modality Motion Movement Mus Mutant Strains Mice Neurobiology Neurologic Neuromodulator Neurons Nicotinic Agonists Nitric Oxide Numbers Oryctolagus cuniculus Output Pathway interactions Pattern Physiological Picrotoxin Play Preparation Presynaptic Terminals Property Proteins Public Health Range Regulation Research Response to stimulus physiology Retina Retinal Retinal Cone Retinal Diseases Role Shaw potassium channel protein family Shunt Device Signal Transduction Somatic Cell Speed Stimulus Stress Stroke Structure Structure-Activity Relationship Synapses Synaptic Transmission Techniques Testing Thinking Time Tracer Translating Translations Trauma Vertebrate Photoreceptors Vision Visual Whole-Cell Recordings Work base cholinergic cohort connexin 36 day deafness experience extracellular gamma-Aminobutyric Acid ganglion cell genetic manipulation horizontal cell insight mutant mouse model nerve supply nervous system disorder neurobiotin neuronal cell body neuroprotection postsynaptic preference prevent research study response retinal neuron retinal rods stem synaptic function transmission process visual process visual processing voltage

项目摘要

DESCRIPTION (provided by applicant): Work over the last decade indicates that electrical synaptic transmission via gap junctions forms an important mode of neuronal communication in the retina. It is now clear that gap junctions are ubiquitous in the retina, being expressed by each of the five major cell classes. In addition, retinal gap junctions have been shown to be dynamically regulated by changes in ambient illumination and circadian rhythms acting through light-activated neuromodulators such as dopamine and nitric oxide. These data suggest that gap junctions play an important role in light adaptation. The long-term goal of our research is define the distribution and function of gap junctions in the mammalian retina so as to define their roles in the processing of visual signals. One specific aim of this proposal is to examine the role of gap junctions in the transmission of rod-mediated signals. Experiments are proposed to study the role of coupling between AII amacrine cells in maintaining the fidelity of the most sensitive rod signals and the role of rod-cone coupling in delivering rod-mediated signals to the horizontal cells. A second aim is to study masked synaptic inputs to retinal neurons, delivered by circuits that utilize gap junctions. Our recent data indicate that rod-mediated synaptic signals to some ganglion cell subtypes are masked in that they are not translated into a spike code and sent to the brain. A second masked input that will be studied is an OFF response in ON direction selective ganglion cells that is delivered by gap junctions made with a subtype of polyaxonal amacrine cells and is normally hidden by inhibitory circuitry. We will determine if masked synaptic inputs in the retina reflect normal dynamics in visual signaling with changing stimulus conditions or a strategy for economic wiring of the retina. A third aim is to study the role of starburst amacrine cell Kv3 potassium channels in generating direction selective responses, a computation whose mechanism has become a classic question in retinal neurobiology. A final aim is to define the structure and function of the 20-30 subtypes of amacrine cells in the mammalian retina to elucidate their roles in generating the output signals of the retina carried by the postsynaptic ganglion cells to the brain. The proposed experiments center on electrophysiological recording of the responses of retinal neurons and their labeling with the gap-permeant biotinylated tracers. The function of gap junctions will be assessed by selectively ablating them either pharmacologically or by knocking out specific connexin proteins in mutant mouse models. Gap junctions have been implicated in a number of neurological diseases including X- linked Charcot-Marie-Tooth disease, nonsyndromic autosomal deafness and neuroprotection following stroke or trauma. Although focused on the function and regulation of gap junctions in mammalian retina, the proposed work will nevertheless provide important insights into the roles of electrical synaptic transmission throughout the brain. PUBLIC HEALTH RELEVANCE: As the most important sense in humans, vision is the modality through which we interact mainly with the world around us. This proposal will examine the role of gap junctions in the retina, which are modulated by light and are thereby likely to play a key role in light adaptation. Gap junctions have been implicated in a number of neurological defects including X-linked Charcot-Marie-Tooth disease, nonsyndromic autosomal deafness and neuroprotection and may play a role in retinopathies related to adaptation and vision under dim ambient light conditions.

描述（由申请人提供）：在过去的十年中工作表明，通过间隙连接的电气突触传播形成了视网膜中神经元通信的重要模式。现在很明显，差距连接在视网膜中无处不在，这是由五个主要细胞类别中的每一个表达的。此外，已经证明，视网膜间隙连接受到通过光激活神经调节剂（如多巴胺和一氧化氮）作用的环境照明和昼夜节律的变化动态调节。这些数据表明，间隙连接在光适应中起着重要作用。我们研究的长期目标是定义哺乳动物视网膜中间隙连接的分布和功能，以定义它们在视觉信号处理中的作用。该提案的一个具体目的是检查间隙连接在杆介导信号传输中的作用。提出了实验来研究AII无链氨酸细胞之间耦合在维持最敏感的杆信号的忠诚度以及杆控制耦合在将杆介导的信号传递到水平细胞中的作用。第二个目的是研究通过使用间隙连接的电路传递的视网膜神经元的掩盖突触输入。我们最近的数据表明，对某些神经节细胞亚型的杆介导的突触信号被掩盖了，因为它们未被翻译成尖峰代码并发送到大脑。将研究的第二个蒙版输入是在方向上的偏离响应选择性神经节细胞，该响应是由用多轴链氨基链氨酸细胞亚型制成的间隙连接传递的，通常被抑制性电路隐藏。我们将确定视网膜中掩盖的突触输入是通过变化的刺激条件或视网膜经济布线的策略反映视觉信号中的正常动态。第三个目的是研究Starburst Amacrine细胞KV3钾通道在产生方向选择性反应中的作用，该计算的机制已成为视网膜神经生物学中的经典问题。最终的目的是定义哺乳动物视网膜中的无长束细胞的20-30个亚型的结构和功能，以阐明其在产生后突触神经节细胞携带的视网膜输出信号中的作用。提出的实验集中于视网膜神经元反应的电生理记录及其与间隙 - 佩格 - 佩格 - 佩格（Gap-Peremant）的生物素化示踪剂的标记。间隙连接的功能将通过在药理学上有选择性地消融或通过在突变小鼠模型中淘汰特定的连接蛋白来评估它们。间隙连接与许多神经系统疾病有关，包括X连接的charcot-marie-tooth疾病，中风或创伤后的非疾病常染色体耳聋和神经保护作用。尽管侧重于哺乳动物视网膜中间隙连接的功能和调节，但拟议的工作仍将为整个大脑电气传播的作用提供重要的见解。公共卫生相关性：作为人类最重要的意义，愿景是我们主要与周围世界互动的方式。该提案将检查差距在视网膜中的作用，该视网膜受到光的调节，因此很可能在光适应中起关键作用。间隙连接已与许多神经系统缺陷有关，包括X连锁的charcot-marie-tooth疾病，非蛋白酶常染色体聋和神经保护性，并可能在昏暗环境光照下与适应性和视力相关的视网膜病变中起作用。