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传递需要数百万个单个突触的建立和维持。这些突触回路不仅要可靠、快速地传输视杆细胞和视锥细胞产生的光诱发信号，而且还必须能够随着白天光照条件的变化而改变。视网膜和大脑中的兴奋性信号是通过突触传递的，而这些突触使用谷氨酸作为它们的神经递质。由于谷氨酸不能穿过脑/血屏障，谷氨酸必须在神经系统中合成。谷氨酸盐/谷氨酸盐再循环系统使突触谷氨酸盐再生。在视网膜中，关于谷氨酰胺如何从Mtiller神经胶质细胞转运回视网膜， 谷氨酸能神经元再合成谷氨酸。提出的研究中心的一个主要目标是确定和表征视网膜中的谷氨酰胺转运机制。 最近发现，与神经元相比，神经胶质细胞不是被动元件，但它们释放调节神经元之间突触传递的神经递质。本研究的第二个目的是鉴定和表征谷氨酸从视网膜中的Muller胶质细胞释放的机制。阐明这些机制在视网膜，一个更易于实验处理的区域的神经系统，将作为一个模型谷氨酸调节中枢神经系统。谷氨酸诱导的兴奋性毒性是许多病理条件如缺血和青光眼产生的变化的基础。神经营养因子调节发育并维持突触活性。缺乏神经营养因子受体TrkB的小鼠的检查显示来自视杆光感受器的突触传递减少。为了消除TrkB缺失对其他体细胞功能的有害影响，Louis Reichardt将使用视网膜特异性 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光诱发视网膜反应的影响。