Mechanisms of Neurotransmisson in Vertebrate Retina

脊椎动物视网膜神经传递机制

• 批准号: 8120736
• 负责人: RUTH HEIDELBERGER
• 金额: $ 35.64万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 2013-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8120736
• 关键词: Address; Affect; Brain Diseases; Calcium; Cell model; Cells; Communication; Complex; Computer Simulation; Consumption; Cyclic AMP; Data; Dementia; Dependence; Development; Dopamine; Endocytosis; Epilepsy; Exhibits; Exocytosis; Funding; Glutamates; Goals; Health; Lighting; Maintenance; Membrane; Modeling; Molecular; Mus; Neuromodulator; Neurons; Output; Pathway interactions; Pattern; Photoreceptors; Play; Positioning Attribute; Process; Proteins; Recovery; Regulation; Research; Rest; Retina; Retinal; Retinal Cone; Retinal Photoreceptors; Role; Schizophrenia; Second Messenger Systems; Series; Signal Transduction; Site; Staging; Synapses; Synaptic Vesicles; System; Testing; Ursidae Family; Vertebrate Photoreceptors; Vesicle; Vision; Vision Disorders; cell type; human disease; insight; meetings; neurotransmitter release; novel; presynaptic; prevent; programs; research study; response; retinal rods; ribbon synapse; second messenger; sensor; transmission process; visual information

DESCRIPTION (provided by applicant): The long-term goal of this research program is to understand the mechanisms by which visual information is transferred across the vertebrate retina. Although the calcium-regulated release of neurotransmitter is a fundamental feature of synaptic communication, the presynaptic mechanisms that govern neurotransmitter release are not yet fully-understood. This is particularly true at the ribbon-style synapses of retinal photoreceptors and bipolar cells, which play pivotal roles in the throughput of visual information. In this research program, we examine mechanisms by which synaptic vesicle dynamics of bipolar cells and photoreceptors of the vertebrate retina are regulated. A combination of biophysical, molecular, and computational approaches are used. Specific goals are to characterize the roles of synaptic vesicle protein 2 (SV2), an integral synaptic vesicle protein, on neurotransmitter release from the mouse rod bipolar cell. A particular emphasis is to define the role of this protein in setting the gain of the rod bipolar cell synapse. The interplay between Ca2+ and other second messengers on the Ca2+-sensitivity of release and vesicle recruitment will also be examined. In addition, the roles of Ca2+ in vesicle recruitment, mobilization and release will be defined for photoreceptors. Detailed computational models of synaptic vesicle mobilization, recruitment and fusion will then be constructed for bipolar cells and photoreceptors. These models will allow us to perform in silico experiments that predict the pattern and extent of neurotransmitter release from various starting conditions. In addition, they will become instrumental in predicting at which step in the complex neuronal secretory pathway a particular manipulation has its effect. Together, the data obtained from this research program will not only reveal new insights into the regulation of the fundamental process of neurotransmitter release at retinal ribbon synapses, but will reveal novel ways by which the release of neurotransmitter is modulated so as to meet the needs of synaptic signaling under different levels of illumination. Furthermore, these results will position us to better determine and understand the role of specific synaptic proteins implicated in disorders of vision. PUBLIC HEALTH RELEVANCE: Results of this research program will enhance our understanding of how we see, providing information for the development of new treatments that will restore vision or prevent its further loss. In addition, it will provide general information about how neurons communicate that is critical for understanding brain diseases such as epilepsy, dementia and schizophrenia.

描述（由申请人提供）：该研究计划的长期目标是了解视觉信息在脊椎动物视网膜上传输的机制。尽管钙调节的神经递质释放是突触通讯的基本特征，但控制神经递质释放的突触前机制尚未完全了解。对于视网膜感光器和双极细胞的带状突触尤其如此，它们在视觉信息的吞吐量中发挥着关键作用。在这个研究项目中，我们研究了双极细胞突触小泡动力学和脊椎动物视网膜光感受器的调节机制。使用生物物理、分子和计算方法的组合。具体目标是表征突触小泡蛋白 2 (SV2)（一种完整的突触小泡蛋白）对小鼠视杆双极细胞释放神经递质的作用。特别强调的是定义该蛋白质在设置杆双极细胞突触增益中的作用。还将检查 Ca2+ 和其他第二信使之间对 Ca2+ 释放敏感性和囊泡募集的相互作用。此外，Ca2+ 在光感受器囊泡募集、动员和释放中的作用也将被定义。然后将为双极细胞和光感受器构建突触小泡动员、募集和融合的详细计算模型。这些模型将使我们能够进行计算机实验，预测各种起始条件下神经递质释放的模式和程度。此外，它们将有助于预测特定操作在复杂的神经元分泌途径的哪一步产生影响。总之，从该研究项目中获得的数据不仅将揭示对视网膜带突触神经递质释放基本过程的调节的新见解，而且将揭示调节神经递质释放以满足神经递质释放的新方法。不同光照水平下的突触信号传导。此外，这些结果将使我们能够更好地确定和理解与视力障碍有关的特定突触蛋白的作用。公共健康相关性：该研究项目的结果将增强我们对我们如何看待事物的理解，为开发恢复视力或防止视力进一步丧失的新疗法提供信息。此外，它将提供有关神经元如何通信的一般信息，这对于理解癫痫、痴呆和精神分裂症等脑部疾病至关重要。