MODULATION OF SYNAPTIC TRANSMISSION

突触传递的调节

• 批准号: 7086843
• 负责人: DAVID Richard COPENHAGEN
• 金额: $ 18.82万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7086843
• 关键词: Urodela; calcium flux; cone cell; dopamine; electroretinography; genetically modified animals; glutamate transporter; glutamates; glutamine; laboratory mouse; neural conduction; neural information processing; neural transmission; neuroregulation; neurotrophic factors; retinal adaptation; rod cell; synapses; synaptogenesis; visual phototransduction; voltage /patch clamp

The detection and signaling of visual information in retina requires the establishment and maintenance of millions of individual synapses. Not only must these synaptic circuits reliably and rapidly transmit the light-evoked signals generated in rods and cones, they must be modifiable as lighting conditions change during the day. Excitatory signals in the retina, and the brain, are transmitted via synapses that use glutamate as their neurotransmitter. Because glutamate does not cross the brain/blood barrier, glutamate has to be synthesized in the nervous system. A glutamate/glutamate recycling system replenishes synaptic glutamate. In retina, little is known about how glutamine is transported out of the Mtiller glial cells and back into the glutamatergic neurons for re-synthesis of glutamate. A principal aim of proposed research centers on identifying and characterizing the glutamine transport mechanisms in retina. Recently it has been discovered that glial cells are not passive elements compared to neurons but they release neurotransmitters that regulate synaptic transmission between neurons. A second aim of this research is to identify and characterize the mechanism(s) by which glutamate is released from Muller glia cells in retina. Elucidating these mechanisms in the retina, a more experimentally tractable region of the nervous system, will serve as a model for glutamate regulation in the CNS. Glutamate-induced excitotoxicity underlies many of the changes produced by pathological conditions such as ischemia and glaucoma. Neurotrophins regulate development and maintain synaptic activity. Examination of mice lacking the neurotrophin receptor TrkB show decreased synaptic transmission from rod photoreceptors. To eliminate deleterious effects that TrkB deletions have on other somatic functions Louis Reichardt will use retina-specific promoters to delete TrkB receptors in the eye only. A third major goal is to characterize the effects of these deletions on light-evoked responses in retina.

视网膜中视觉信息的检测和信号需要建立和维护数百万个个人突触。这些突触电路不仅必须可靠，快速地传输杆和锥体中产生的光诱发信号，而且由于白天的照明条件发生变化，它们必须进行修改。视网膜和大脑中的兴奋性信号是通过使用谷氨酸作为神经递质的突触传播的。由于谷氨酸不跨越大脑/血液屏障，因此必须在神经系统中合成谷氨酸。谷氨酸/谷氨酸回收系统补充突触谷氨酸。在视网膜中，关于如何将谷氨酰胺从mtiller神经胶质细胞中运出并回到 谷氨酸能神经元，用于谷氨酸的重新合成。拟议研究的主要目的是识别和表征视网膜中谷氨酰胺运输机制。 最近，已经发现，与神经元相比，神经胶质细胞不是被动元素，而是释放了调节神经元之间突触传播的神经递质。这项研究的第二个目的是识别和表征从视网膜中穆勒胶质细胞释放谷氨酸的机制。阐明视网膜中的这些机制，即神经系统的一个更具实验性处理的区域，将作为中枢神经系统中谷氨酸调节的模型。谷氨酸诱导的兴奋性毒性基于缺血和青光眼等病理状况产生的许多变化。神经营养蛋白调节发育并维持突触活性。缺乏神经营养蛋白受体TRKB的小鼠的检查显示，杆感光体的突触传播降低。为了消除TRKB缺失对其他躯体功能的有害影响 启动子仅删除眼睛中的TRKB受体。第三个主要目标是表征这些缺失对视网膜中诱发的响应的影响。