Dynamic modulation of retinal ribbon-type synapses

视网膜带状突触的动态调制

基本信息

批准号：
8064670
负责人：
HENRIQUE Prado VON GERSDORFF
金额：
$ 32.93万
依托单位：
OREGON HEALTH & SCIENCE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-05-01 至 2013-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8064670
关键词：
AMPA Receptors ATP phosphohydrolase Acidity Affect Affinity Amacrine Cells Animals Biochemical Biological Assay Brain Carrier Proteins Cells Chloride Channels Chloride Ion Chlorides Computer Simulation Coupling Cytosol Data Devices Electric Capacitance Electrophysiology (science)Endocytosis Excision Exocytosis Feedback Funding Future GABA Receptor GABA transporter Glutamate Transporter Glutamates Goldfish In Situ Indium Inner Plexiform Layer Kinetics Lead Life Light Measurement Measures Mediating Membrane Membrane Potentials Mental Depression Modeling Monitor Morphology Nerve Neurons Output Pattern Photoreceptors Presynaptic Receptors Presynaptic Terminals Process Property Prosthesis Protons Pump Recovery Recycling Research Research Personnel Residual state Resolution Retina Retinal Retinal Diseases Role Signal Pathway Slice Synapses Synaptic Cleft Synaptic Transmission Synaptic Vesicles Techniques Testing Time Vesicle Vision Visual Visually Impaired Persons Work channel blockers computerized data processing desensitization design gamma-Aminobutyric Acid ganglion cell insight neurotransmitter release pH gradient patch clamp postsynaptic premature presynaptic programs receptor research study retinal prosthesis ribbon synapse synaptic depression time use visual information

项目摘要

DESCRIPTION: The retina detects and transmits large amounts of visual information quickly and reliably. Ribbon synapses are key components of the vertebrate retinal circuitry, forming the first and second presynaptic elements in the signaling pathway to the brain. The specialized morphology and function of the ribbons presumably endows them with a unique capacity for copious and fast neurotransmitter release, which is thought to be essential for the efficient processing and encoding of visual information. Nevertheless, the underlying cellular mechanisms that modulate and maintain transmitter output from ribbon synapses under vastly different ambient light conditions are poorly understood. Due to their large size, we are able to patch-clamp single goldfish bipolar cell terminals. This allows us to measure both presynaptic Ca currents and evoked changes in membrane capacitance that assay synaptic vesicle exocytosis and endocytosis in real time from a living nerve terminal. We have found that the reciprocal synapse of bipolar cells undergoes short-term synaptic depression. We will determine the underlying mechanisms responsible for this depression. The first hypothesis to be tested is that synaptic vesicle pool depletion at GABAergic amacrine cells, and desensitization of GABAA and AMPA receptors, contribute to depression and largely determine the recovery rate. We also find that bipolar cell terminals have a tonic inhibitory current mediated by high affinity GABAC receptors that do not desensitize. Thus the second hypothesis is that different subtypes GABA transporters in amacrine cells set the level of this tonic inhibitory current. We also have preliminary evidence that the acidity of synaptic vesicles and the process of filling synaptic vesicles with glutamate may involve chloride channels on the vesicle membrane. Biochemical studies of this process are controversial and few studies have been done in intact nerve terminals. We will thus study this process in the bipolar cell terminal embedded in a retinal slice. These studies should increase our basic understanding of signal processing in the retina and they may be relevant to retinal diseases that degenerate photoreceptors, but spare ganglion cells. A prosthetic device that stimulates the remaining neurons might restore some sight to blind people. However, this stimulation has to encode visual information at the same high rates that bipolar cells do in normal retinas. A better understanding of how bipolar cells release glutamate to excite ganglion cells will thus lead to insights on how to develop a retinal prosthesis using more physiologically relevant patterns of stimulation that match more closely the original information rates of bipolar cells. Our studies will thus hopefully aid in the future design of more efficient retinal prosthesis devices.

描述：视网膜检测和传输大量视觉信息。色带突触是脊椎动物视网膜电路的关键组成部分，在通往大脑的信号传导途径中形成了第一和第二突触的元素。丝带的专业形态和功能大概赋予了它们独特的大量和快速神经递质释放的能力，这对于有效的视觉信息处理和编码是必不可少的。然而，在遥不可及的环境光条件下调节和维持丝带突触的发射机输出的基本细胞机制知之甚少。由于它们的尺寸较大，我们能够补丁夹单金鱼双极细胞端子。这使我们能够测量突触前CA电流和诱发膜电容的变化，从活神经末端分析突触囊泡外胞毒性和内吞作用。我们发现，双极细胞的相互突触会经历短期突触抑制。我们将确定负责这种抑郁症的基本机制。要测试的第一个假设是，Gabaergic amacrine细胞处的突触囊泡池消耗以及GABAA和AMPA受体的脱敏，会导致抑郁症，并在很大程度上决定了回收率。我们还发现，双极细胞末端具有不脱敏的高亲和力GABAC受体介导的滋补抑制电流。因此，第二个假设是无链氨酸细胞中的不同亚型GABA转运蛋白设置了这种补品抑制电流的水平。我们还有初步证据表明，突触囊泡的酸度和用谷氨酸填充突触囊泡的过程可能涉及囊泡膜上的氯化物通道。这一过程的生化研究是有争议的，在完整的神经末端进行了很少的研究。因此，我们将在视网膜切片中嵌入的双极细胞末端研究此过程。这些研究应增加我们对视网膜信号处理的基本理解，它们可能与退化感光体但备用神经节细胞的视网膜疾病有关。刺激其余神经元的假体装置可能会恢复对盲人的视力。但是，这种刺激必须以与正常视网膜中双极细胞相同的高速率编码视觉信息。因此，更好地理解双极细胞如何释放谷氨酸以激发神经节细胞，从而使如何使用更多与生理相关的刺激模式来开发视网膜假体的见解，从而更匹配双极细胞的原始信息速率。因此，我们的研究将有望帮助未来的视网膜假体设备设计。