VISUAL SIGNALLING IN RETINA

我们打算研究哺乳动物视网膜中的视觉信号。 一组 的实验将集中在视觉转导，而第二个将 集中在神经电路，通过其转导信号流到 视网膜神经节细胞 关于视觉传导的实验将检查仍然很差的- 终止对光的反应的过程。 通过使 转基因小鼠视杆细胞和正常小鼠视杆细胞的电记录 灵长类光感受器，我们会问： 1.视紫红质必须在其C末端区域磷酸化， 催化活性在体内正常关闭？什么时候 磷酸化发生？在单个位点的磷酸化是否足以 导致完全关闭 2.抑制蛋白必须与磷酸化视紫红质结合才能完全关闭吗？ arrestin什么时候绑定？磷酸化单独减少了多少 催化活性？ 3.调节视紫红质的钙结合蛋白recoverin 关闭，使单光子响应可再现，调节增益 减少发生在背景光，或两者兼而有之？ 4.视紫红质中的什么分子缺陷导致了- 正常灵长类视杆细胞的长时间单光子反应是 老年人视紫红质更有可能是有缺陷的？ 5.灵长类视锥细胞内钙的动态是什么， 它们是否与锥体闪光反应的双相波形有关？ 神经回路的实验将使用多电极阵列， 记录从神经节细胞在分离的灵长类动物视网膜。我们会问： 6.神经节细胞群的感受野是如何取样的 视觉图像？ 7.灵长类动物视网膜的神经节细胞经历协同放电还是 它们只发出独立的信号吗 如果存在协同射击， 细胞参与，在什么长度尺度上信号相关， 协同发射如何有助于对比度的检测， 颜色？ 8.什么是神经节细胞感受野的贡献 光感受器和水平细胞反馈之间的电耦合 对感光细胞的影响 9.视锥细胞本身是否是色适应的主要部位？ 视网膜，还是下游细胞也参与其中？ 一个锥体的罐适应性 类改变信号的增益从另一个锥类？

We propose to study visual signalling in the mammalian retina. One group of experiments will focus on visual transduction, while a second will focus on the neural circuits over which transduced signals flow to the retinal ganglion cells. The experiments on visual transduction will examine the still poorly- understood processes that terminate the response to light. By making electrical recordings from transgenic mouse rods as well as normal primate photoreceptors we will ask: 1. Must rhodopsin be phosphorylated in the C terminal region for its catalytic activity to shut off normally in vivo? When does phosphorylation occur? Is phosphorylation at a single site sufficient to elicit complete shutoff? 2. Must arrestin bind to phosphorylated rhodopsin to complete shut-off? When does arrestin bind? How much does phosphorylation alone reduce catalytic activity? 3. Does the Ca-binding protein recoverin, which regulates rhodopsin shutoff, make the single photon response reproducible, mediate the gain reduction that occurs in background light, or both? 4. What molecular defect in rhodopsin is responsible for the anomalously- prolonged single photon responses that occur in normal primate rods? Is older rhodopsin more likely to be defective? 5. What are the dynamics of intracellular Ca in primate cones, and how do they relate to the diphasic waveform of the cone flash response? The experiments on neural circuitry will use a multielectrode array to record from ganglion cells in isolated primate retinas. We will ask: 6. How do the receptive fields of populations of ganglion cells sample visual images? 7. Do ganglion cells in the primate retina undergo concerted firing or do they only signal independently? If concerted firing is present, what cells are involved, over what length scale are signals correlated, and how does concerted firing contribute to the detection of contrast and color? 8. What is the contribution to ganglion cell receptive fields of electrical coupling between photoreceptors and horizontal cell feedback on photoreceptors? 9. Are the cones themselves the dominant site of chromatic adaptation in the retina, or are downstream cells involved? Can adaptation of one cone class change the gain of signals from another cone class?