MODULATION OF SYNAPTIC TRANSMISSION

视网膜中视觉信息的检测和信号传递需要数百万个单独的突触的建立和维护。这些突触回路不仅要可靠、快速地传递杆状细胞和视锥细胞产生的光诱发信号，还必须随着白天光照条件的变化而改变。视网膜和大脑中的兴奋信号通过突触传递，突触使用谷氨酸作为神经递质。因为谷氨酸不能穿过脑/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，对于谷氨酰胺是如何从米勒神经胶质细胞转运到视网膜的，我们所知甚少

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.