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整个脊椎动物视网膜上传递的机制。尽管神经递质的钙调节释放是突触通信的基本特征，但控制神经递质释放的突触前机制尚未完全理解。在视网膜光感受器和双极细胞的带状突触中尤其如此，这些突触在视觉信息的吞吐量中起关键作用。在该研究计划中，我们研究了双极细胞的突触囊泡动力学和脊椎动物视网膜的感光体的机制。使用了生物物理，分子和计算方法的组合。具体目标是表征突触囊泡蛋白2（SV2）（一种积分囊泡蛋白）在从小鼠杆双极细胞中释放神经递质中的作用。一个特别的重点是定义该蛋白质在设定杆双极细胞突触增益方面的作用。还将检查Ca2+与其他第二个使者之间的相互作用在Ca2+释放和囊泡募集的敏感性上。另外，Ca2+在囊泡募集中的作用，动员和释放将定义为感光体。然后将为双极细胞和感光体构建突触囊泡动员，募集和融合的详细计算模型。这些模型将使我们能够在计算机实验中执行，以预测神经递质从各种起始条件中释放的模式和程度。此外，它们将在预测复杂神经元分泌途径的哪个步骤中发挥作用，特定操纵具有其作用。总之，从该研究计划获得的数据不仅会揭示对视网膜色带突触下神经递质释放基本过程的调节的新见解，而且还将揭示神经递质释放的新方法，以调制神经递质的释放，以满足不同照明水平下突触信号的需求。此外，这些结果将使我们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。公共卫生相关性：该研究计划的结果将增强我们对如何看待的理解，为开发新疗法提供信息，以恢复视力或防止其进一步的损失。此外，它将提供有关神经元如何沟通的一般信息，这对于理解脑疾病，例如癫痫，痴呆和精神分裂症至关重要。