MODULATION OF SYNAPTIC TRANSMISSION

视网膜中视觉信息的检测和信号传递需要建立和维持数百万个单独的突触。这些突触电路不仅必须可靠而快速地传输由视杆和视锥产生的光诱发信号，而且它们还必须随着白天照明条件的变化而改变。视网膜和大脑中的兴奋信号是通过突触传递的，突触使用谷氨酸作为神经递质。因为谷氨酸不会穿过大脑/血液屏障，所以谷氨酸必须在神经系统中合成。谷氨酸/谷氨酸循环系统补充突触谷氨酸。在视网膜中，谷氨酰胺是如何从Mtiller神经胶质细胞转运回视网膜的，人们知之甚少。 谷氨酸能神经元用于谷氨酸的重新合成。拟议研究的一个主要目的是识别和表征视网膜中谷氨酰胺的运输机制。 最近发现，与神经元相比，神经胶质细胞并不是被动的成分，而是释放神经递质来调节神经元之间的突触传递。这项研究的第二个目的是鉴定和表征视网膜穆勒胶质细胞释放谷氨酸的机制(S)。视网膜是神经系统中一个更易于实验处理的区域，阐明这些机制将成为中枢神经系统谷氨酸调节的模型。谷氨酸诱导的兴奋性毒性是缺血和青光眼等病理条件产生的许多变化的基础。神经营养因子调节发育和维持突触活动。对缺乏神经营养素受体TrkB的小鼠的检查显示，杆状光感受器的突触传递减少。为了消除TrkB缺失对其他躯体功能的有害影响，Louis Reichardt将使用特定于视网膜的 启动子只删除眼睛中的TrkB受体。第三个主要目标是描述这些缺失对视网膜光诱发反应的影响。

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.