Functional analysis of retinal inhibitory processes

视网膜抑制过程的功能分析

• 批准号: 8531940
• 负责人: Jozsef Vigh
• 金额: $ 29.13万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-01 至 2015-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8531940
• 关键词: Affect; Amacrine Cells; Architecture; Area; Axon; Binding Sites; Bypass; Calcium; Calcium Channel; Cells; Characteristics; Code; Color; Complex; Data; Dendrites; Detection; Devices; Electric Capacitance; Environment; Equilibrium; Feedback; Glutamates; Glycine; Goals; Goldfish; Health; Human; Image; In Situ; Ion Channel; Kinetics; Lateral; Light; Light Adaptations; Measurement; Measures; Mediating; Membrane; Membrane Potentials; Motion; N-Methyl-D-Aspartate Receptors; Output; Photoreceptors; Physiological; Preparation; Presynaptic Terminals; Process; Prosthesis; Receptor Activation; Regulation; Research; Resolution; Retina; Retinal; Role; Shapes; Signal Transduction; Slice; Synapses; Synaptic Potentials; Testing; Time; Translating; Vision; Visual; Visually Impaired Persons; Work; cell preparation; computerized data processing; design; gamma-Aminobutyric Acid; ganglion cell; information processing; interest; neural circuit; neuronal cell body; patch clamp; receptive field; receptor function; relating to nervous system; research study; response; visual information; voltage; voltage gated channel

DESCRIPTION (provided by applicant): Retinal inhibitory inputs shape the kinetics of graded, sustained photoreceptor signals as they pass through the retina. At the network level, retinal inhibition mediates the antagonistic center-surround organization of the bipolar cell's receptive field, and in turn, that of the ganglion cell. This retinal circuit underlies contrast detection, a fundamental feature of signal processing by the retina. The goal of the proposed research is to study the distribution, functional characteristics and regulation of inhibitory inputs targeting an identified retinal bipolar cell. I will take advantage of a unique preparation made from the goldfish retina, in which patch-clamp recordings of light evoked membrane currents can be made either from the soma or the axon terminal of an ON-type, Mb bipolar cell in a slice preparation. Stable recordings from these compartments is possible even after axon severing, thus outer or inner retinal inhibitory inputs can be separately studied. Using this preparation I will revisit fundamental questions of visual information processing in the vertebrate retina. My preliminary data show that light evokes different responses at the bipolar cell soma compared to the axon terminal, due to differences in their respective synaptic inputs and voltage-gated channels. The first specific aim will characterize the light-evoked responses of the axon terminal in intact Mb bipolar cells and will study with high time-resolution capacitance measurements how these physiological responses trigger glutamate release. The second specific aim will focus on separating outer and inner retinal inhibition targeting Mb bipolar cells. I will determine how each influence the glutamate output, and separate their contributions to the antagonistic surround response. I recorded light-evoked inhibitory synaptic currents from bipolar axon terminals with severed axons, which represents pure lateral inhibition. I will characterize electrophysiologically and pharmacologically these synaptic inputs at various light adaptation levels, and determine their underlying synaptic circuitry. I have preliminary evidence that NMDA receptors provide enough calcium to trigger GABA release from amacrine cells directly and locally, bypassing voltage-gated calcium channels. The last specific aim will test the hypothesis that NMDA receptor regulation in amacrine cells influences synaptically triggered GABA release and in turn, bipolar cell output. Overall, these experiments will use a combination of capacitance, membrane potential/ current measurements and pharmacological manipulations to determine how the excitatory visual information reaching the ganglion cells is regulated by progressive levels of inhibition as the signal passes through the retinal network. PUBLIC HEALTH RELEVANCE: Images of the environment are translated into neural codes by all vertebrate retinas, including that of humans, in a very similar manner: the retina codes for contours, colors and motion. The proposed research investigates the natural mechanisms underlying contour detection. The results can be used to guide the design of prosthetic vision devices to restore some sight to blind people.

描述（由申请人提供）：视网膜抑制输入塑造了经过视网膜时分级，持续的光感受器信号的动力学。在网络水平上，视网膜抑制介导了双极细胞的接收场的拮抗中心旋转组织，进而介导了神经节细胞的拮抗中心。该视网膜电路是对比检测的基础，这是视网膜信号处理的基本特征。拟议研究的目的是研究针对鉴定出的视网膜双极细胞的抑制投入的分布，功能特征和调节。我将利用来自金鱼视网膜制成的独特制剂，其中可以通过soma或型号的MB双极单元在切片制备中制成光诱发的膜电流的贴片钳记录。即使在轴突断开后，这些隔室的稳定记录也是可能的，因此可以分别研究外部或内部视网膜抑制输入。使用此准备，我将重新审视脊椎动物视网膜视觉信息处理的基本问题。我的初步数据表明，由于其各自的突触输入和电压门控通道的差异，光线与轴突末端相比唤起了双极细胞体内的不同反应。第一个具体目的将表征完整的MB双极细胞中轴突末端的光诱发响应，并将通过高时间分辨率的电容测量进行研究，这些生理反应如何触发谷氨酸。第二个特定目的将集中于分离靶向MB双极细胞的外部和内部视网膜抑制作用。我将确定每种情况如何影响谷氨酸的产量，并将它们对拮抗周围响应的贡献分开。我记录了带有切断轴突的双极轴突末端的光诱发的抑制性突触电流，这代表了纯侧抑制。我将在电生理学和药理学上表征这些突触输入在各种光适应水平上，并确定其潜在的突触电​​路。我有初步的证据表明，NMDA受体提供足够的钙来触发GABA直接和局部从局部释放的GABA，从而绕过电压门控钙通道。最后一个特定目的将检验以下假设：无长4mda受体调节会影响突触触发的GABA释放，然后又影响双极细胞输出。总体而言，这些实验将结合电容，膜电位/电流测量和药理学操作，以确定如何到达神经节细胞的兴奋性视觉信息，随着信号通过视网膜网络的逐步抑制水平。公共卫生相关性：环境图像以非常相似的方式将所有脊椎动物视网膜（包括人类）转化为神经代码：轮廓，颜色和运动的视网膜代码。拟议的研究调查了轮廓检测基础的自然机制。结果可用于指导假肢视觉设备的设计，以恢复盲人的视力。

项目成果

Dopaminergic amacrine cells express opioid receptors in the mouse retina.

• DOI: 10.1017/s0952523812000156
• 发表时间: 2012-05
• 期刊: VISUAL NEUROSCIENCE
• 影响因子: 1.9
• 作者: Gallagher, Shannon K.;Anglen, Julia N.;Mower, Justin M.;Vigh, Jozsef
• 通讯作者: Vigh, Jozsef

Light-evoked S-nitrosylation in the retina.

• DOI: 10.1002/cne.23780
• 发表时间: 2015-10-01
• 期刊: The Journal of comparative neurology
• 作者: Tooker RE;Vigh J
• 通讯作者: Vigh J

Quantifying the effect of light activated outer and inner retinal inhibitory pathways on glutamate release from mixed bipolar cells.

量化光激活的外部和内部视网膜抑制途径对混合双极细胞谷氨酸释放的影响。

• DOI: 10.1002/syn.22028
• 发表时间: 2018
• 期刊: Synapse (New York, N.Y.)
• 作者: Lipin,MikhailY;Vigh,Jozsef
• 通讯作者: Vigh,Jozsef

Glycine transporter 1 modulates GABA release from amacrine cells by controlling occupancy of coagonist binding site of NMDA receptors.

甘氨酸转运蛋白 1 通过控制 NMDA 受体共激动剂结合位点的占用来调节无长突细胞释放 GABA。

• DOI: 10.1152/jn.00193.2013
• 发表时间: 2013
• 期刊: Journal of neurophysiology
• 影响因子: 2.5
• 作者: Rozsa,Eva;Vigh,Jozsef
• 通讯作者: Vigh,Jozsef

Nitric oxide mediates activity-dependent plasticity of retinal bipolar cell output via S-nitrosylation.

一氧化氮通过 S-亚硝基化介导视网膜双极细胞输出的活动依赖性可塑性。

• DOI: 10.1523/jneurosci.2792-13.2013
• 发表时间: 2013
• 期刊: The Journal of neuroscience : the official journal of the Society for Neuroscience
• 作者: Tooker,RyanE;Lipin,MikhailY;Leuranguer,Valerie;Rozsa,Eva;Bramley,JayneR;Harding,JacquelineL;Reynolds,MelissaM;Vigh,Jozsef
• 通讯作者: Vigh,Jozsef