Dynamic modulation of retinal ribbon-type synapses

视网膜带状突触的动态调制

• 批准号: 7383768
• 负责人: HENRIQUE Prado VON GERSDORFF
• 金额: $ 33.96万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7383768
• 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; Chromosome Pairing; Computer Simulation; Condition; 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; Localized; 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; Range; Rate; 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; Thinking; 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; presynaptic; programs; receptor; research study; retinal prosthesis; ribbon synapse; size; synaptic depression; time use; visual information

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：视网膜快速可靠地检测和传输大量视觉信息。带状突触是脊椎动物视网膜回路的关键组成部分，形成通往大脑的信号通路中的第一和第二突触前元件。带状物的特殊形态和功能可能赋予它们丰富而快速的神经递质释放的独特能力，这被认为是有效处理和编码视觉信息所必需的。然而，在截然不同的环境光条件下，调节和维持带状突触发射器输出的潜在细胞机制却知之甚少。由于它们的大尺寸，我们能够膜片钳单个金鱼双极细胞终端。这使我们能够测量突触前钙电流和诱发的膜电容的变化，测定突触囊泡胞吐和胞吞作用在真实的时间从一个活的神经末梢。 我们已经发现双极细胞的相互突触经历短期突触抑制。我们将确定这种抑郁症的潜在机制。要检验的第一个假设是GABA能无长突细胞的突触囊泡池耗尽，以及GABAA和AMPA受体的脱敏，有助于抑郁症，并在很大程度上决定了恢复率。我们还发现双极细胞末端具有由不脱敏的高亲和力GABAC受体介导的紧张性抑制电流。因此，第二个假设是，在无长突细胞中的不同亚型GABA转运体设置了这种紧张性抑制电流的水平。我们也有初步的证据表明，突触囊泡的酸性和谷氨酸填充突触囊泡的过程可能涉及囊泡膜上的氯离子通道。这一过程的生化研究是有争议的，很少有研究在完整的神经末梢。因此，我们将研究这一过程中的双极细胞终端嵌入视网膜切片。这些研究应该增加我们对视网膜信号处理的基本理解，它们可能与视网膜疾病有关，这些疾病使光感受器退化，但保留了神经节细胞。一种刺激剩余神经元的假肢装置可能会使盲人恢复一些视力。然而，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来刺激神经节细胞，将有助于了解如何使用更接近双极细胞原始信息速率的生理相关刺激模式来开发视网膜假体。因此，我们的研究将有望有助于未来设计更有效的视网膜假体设备。