Cellular Neurobiology of the Retina

视网膜细胞神经生物学

• 批准号: 7364319
• 负责人: GARY G MATTHEWS
• 金额: $ 38.56万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 1981
• 资助国家: 美国
• 起止时间: 1981-08-01 至 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7364319
• 关键词: Affect; Biological; Brain; C-Terminal Binding Protein 1; Cells; Cellular Neurobiology; Chromosome Pairing; Clathrin; Complex; Dissection; Dynamin; Electron Microscopy; Electrophysiology (science); Endocytosis; Equilibrium; Exocytosis; Fatigue; Generations; Genes; Goals; Goldfish; Kinetics; Knowledge; Label; Life; Light; Location; Mediating; Membrane; Metabotropic Glutamate Receptors; Methods; Molecular; Monitor; Movement; Mus; Natural regeneration; Neurons; Neurotransmitters; Optics; Output; Pathway interactions; Peptides; Photoreceptors; Physiological; Play; Presynaptic Terminals; Process; Proteins; Range; Rate; Regulation; Regulatory Element; Reporter; Resolution; Rest; Retina; Retinal; Retrieval; Role; Salamander; Signal Transduction; Structure; Synapses; Synaptic Vesicles; Techniques; Testing; Time; Transgenic Mice; Translating; Vesicle; Vision; Visual; Visual system structure; Work; base; chemical release; cytomatrix; fluorescence imaging; genetic manipulation; grasp; mouse model; neurotransmitter release; presynaptic; protein protein interaction; rab3A GTP-Binding Protein; recombinase; research study; retinal bipolar neuron; retinal rods; ribbon synapse; size; stem; synaptic function; transmission process; visual information; visual process; visual processing

DESCRIPTION: The photoreceptor cells of the retina carry out the essential task of translating light into electrical signals, which are then transmitted to retinal bipolar neurons for further analysis before being communicated to the rest of the visual system. All visual information must pass through this obligatory pathway, which involves two synaptic relays, one from photoreceptors to bipolar cells, and another from bipolar cells to third-order neurons of the inner retina. Both of these through-conducting synapses are specialized for continuous release of chemical neurotransmitter, which is required for the proper transmission of visual information. Despite their crucial role in vision, these unique photoreceptor and bipolar-cell synapses remain poorly understood, and it is not yet known how they are able to support high rates of neurotransmitter release for prolonged periods, while other synapses in the brain fatigue rapidly during sustained stimulation. This project will use a combination of cellular electrophysiology and high-resolution fluorescence imaging to provide the first complete picture of the synaptic vesicle cycle at the special synapses of retinal bipolar neurons and photoreceptor cells. The vesicle cycle can be broken down into several components: rapid fusion of synaptic vesicles to initiate transmitter release, resupply of releasable vesicles to support continued release, movement of vesicles to and from reserve and releasable pools, compensatory endocytosis to retrieve fused vesicles, and regeneration of new releasable vesicles after endocytosis. The specific aims of the project exploit the ability to tag synaptic vesicles and synaptic active zones with distinct fluorescent labels to observe directly the vesicle movements that underlie all these components of the vesicle cycle. Then, genetic manipulations and selective protein interference will be used to unravel the molecular machinery that gives retinal synapses the unique ability to release neurotransmitter continuously and allows them to perform their central role in transmitting visual signals. The results will provide essential new information about how the visual signals arising in the photoreceptor cells are ultimately transmitted to the rest of the brain.

描述：视网膜的感光细胞执行将光转化为电信号的基本任务，然后将其传输到视网膜双极神经元进行进一步分析，然后再传递到视觉系统的其余部分。所有视觉信息都必须通过这条必经途径，该途径涉及两个突触中继，一个从光感受器到双极细胞，另一个从双极细胞到内视网膜的三级神经元。这两个直通突触专门用于持续释放化学神经递质，这是正确传输视觉信息所必需的。尽管它们在视觉中发挥着至关重要的作用，但这些独特的光感受器和双极细胞突触仍然知之甚少，而且尚不清楚它们如何能够长时间支持神经递质的高速率释放，而大脑中的其他突触在持续的持续时间内迅速疲劳。刺激。该项目将结合细胞电生理学和高分辨率荧光成像，提供视网膜双极神经元和感光细胞特殊突触处突触小泡周期的第一张完整图片。囊泡循环可分为几个部分：突触囊泡的快速融合以启动递质释放，可释放囊泡的再供应以支持持续释放，囊泡往返于储备池和可释放池的运动，补偿性内吞作用以恢复融合的囊泡，以及再生内吞作用后新释放的囊泡。该项目的具体目标是利用利用不同荧光标记来标记突触小泡和突触活性区的能力，以直接观察囊泡周期所有这些组成部分背后的囊泡运动。然后，基因操作和选择性蛋白质干扰将被用来解开分子机制，使视网膜突触具有持续释放神经递质的独特能力，并使其能够在传递视觉信号中发挥核心作用。研究结果将提供关于感光细胞中产生的视觉信号如何最终传输到大脑其他部分的重要新信息。