RETINAL SYNAPTIC TRASMISSION--CA++ AND NEUROTRASMITTERS

视网膜双极细胞终末递质释放的调节 对于从外层视网膜到视网膜的视觉信号处理是重要的。 脊椎动物的内层视网膜。 虽然Ca 2+在 突触前末梢的递质释放是公认的， 细胞内Ca ~（2+）浓度（[Ca ~（2+）]i）在 突触前终末及其对递质释放的影响仍然是 基本上不清楚。本提案的目的是研究 钙通道和GABA受体对钙动力学的调节 在哺乳动物双极细胞的轴突末端。实验将 在单独的大鼠和小鼠双极细胞中进行。钙敏感 将使用荧光染料。 将监测荧光信号 通过基于高分辨率共焦显微镜的成像系统。细胞的 膜电位将通过膜片钳方法控制， 或者，高K+将诱发细胞去极化。的 具体目标是：（一）确定空间分布 双极细胞中不同类型的Ca 2+通道; 2）表征 双极细胞终末的Ca 2+瞬变在激活过程中， 不同的Ca 2+通道和细胞去极化过程中， 双极光响应波形; 3）表征不同的 GABA A和GABA C受体对Ca ~（2+）调节的作用 双极细胞终端的瞬变; 4）确定空间 GABA受体的分布和可能的共定位 特定类型的GABA受体与特定类型的Ca 2 + 渠道我们从这些研究中获得的知识不仅会导致 更好地理解基本的视觉信号处理， 哺乳动物视网膜，但也将有助于我们的知识的作用， 突触传递中的Ca ~（2+）和抑制性神经递质 CNS。

The regulation of transmitter release at retinal bipolar cell terminals is important for visual signal processing from the outer retina to the inner retina in vertebrates. Although the central role of Ca2+ in transmitter release at presynaptic terminals is well established, the dynamic regulation of intracellular Ca2+ concentrations ([Ca2+]i) at presynaptic terminals and its effect on transmitter release is still largely unclear. The objective of this proposal is to study the roles of Ca2+ channels and GABA receptors in the regulation of Ca2+ dynamics at the axon terminal of mammalian bipolar cells. Experiments will be performed in solitary rat and mouse bipolar cells. Ca2+-sensitive fluorescence dyes will be used. Fluorescence signals will be monitored by a high resolution confocal microscope based imaging system. Cell's membrane potential will be controlled by patch-clamp methods and, alternatively, cell depolarization will be evoked by high K+. The specific aims are: I) to determine the spatial distribution of different types of Ca2+ channels in bipolar cells; 2) to characterize the Ca2+ transients at bipolar cell terminals during the activation of different Ca2+ channels and during cell depolarization that mimics bipolar light response waveforms; 3) to characterize the distinct effects of GABA A and GABA C receptors on the regulation of the Ca2+ transients at bipolar cell terminals; 4) to determine the spatial distribution of GABA receptors and the possible co-localization of specific types of GABA receptors with specific type(s) of Ca2+ channels. The knowledge we gain from these studies will not only lead to a better understanding of basic visual signal processing in mammalian retina but will also contribute to our knowledge of the roles of Ca2+ and inhibitory neurotransmitters in synaptic transmission in the CNS.