MECHANISMS OF NEUROTRANSMISSION IN VERTEBRATE RETINA

脊椎动物视网膜的神经传递机制

• 批准号: 6179014
• 负责人: RUTH HEIDELBERGER
• 金额: $ 10.38万
• 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 2003-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6179014
• 关键词: adenosine triphosphate; alternatives to animals in research; calcium; calcium channel; cyclic AMP; endocytosis; exocytosis; flash photolysis; goldfish; membrane activity; neural information processing; neural transmission; neurotransmitters; protein kinase; retinal bipolar neuron; second messengers; synaptic vesicles; visual stimulus; voltage gated channel

Calcium-regulated release of neurotransmitter is a fundamentally important process throughout the central nervous system. How this process is regulated presynaptically is not yet fully understood, but recent advances in the detection of synaptic vesicle fusion and neurotransmitter release, combined with the identification of putative proteins that either comprise or interact with the secretion machinery have now made such mechanistic investigations feasible. The long-range goal of this research project is to understand how the transfer of visual information between the outer and inner retina is regulated at the presynaptic level in retinal bipolar cells. The approach is to use a combination of biophysical techniques, including measurements of membrane capacitance and flash-photolysis of caged-calcium, in conjunction with probes designed to interact with SNARE proteins, to identify distinct stages of the secretion pathway in single synaptic terminals of retinal bipolar cells. The results of these experiments will guide the formation of a testable model of the late steps in neurotransmitter exocytosis at a ribbon synapse. Then, modulation of this secretory pathway by physiologically relevant neurotransmitters, neuropeptides, and second messenger systems will be examined to determine the extent to which they modulate synaptic release. Calcium, in addition to its role in initiating release, may effect other parts of the secretory pathway. Therefore, the actions of calcium and calcium- activated conductances on synaptic release and synaptic vesicle cycling will also be examined. Armed with this information, predictions will be made about the effects of local circuit interactions and previous stimulus history on the throughput of visual information from photoreceptors to the third-order neurons of the retina.

钙调节的神经递质的释放是从根本上 整个中枢神经系统的重要过程。 如何 过程受到调节前的调节，尚未完全理解，但是 检测突触囊泡融合的最新进展和 神经递质释放，结合了推定的鉴定 构成或与分泌机械相互作用的蛋白质 现在使这种机械研究可行。 远程 该研究项目的目标是了解如何转移 外部视网膜和内部视网膜之间的视觉信息受到调节 视网膜双极细胞中的突触前水平。 方法是使用 生物物理技术的结合，包括测量 在 与旨在与SNARE蛋白相互作用的探针结合 确定单个突触中分泌途径的不同阶段 视网膜双极细胞的末端。 这些实验的结果 将指导形成后期步骤的可测试模型 丝带突触时神经递质胞吐作用。 然后，调制 生理上相关的神经递质的这种分泌途径， 将检查神经肽和第二信使系统 确定它们调节突触释放的程度。 钙， 除了其在发行释放中的作用外，还可能影响其他部分 分泌道路。因此，钙和钙的作用 突触释放和突触囊泡循环时激活的电导 也将被检查。 有了这些信息，预测将 关于本地电路相互作用和以前的影响 关于视觉信息的刺激历史 视网膜三阶神经元的感光体。