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 的实验将专注于视觉转导，而第二个实验将 重点放在神经电路上，通过这些神经电路，被转换的信号流到 视网膜神经节细胞。 视觉转导的实验将检验仍然很差的- 理解终止对光的反应的过程。通过制作 转基因小鼠杆和正常小鼠的电记录 灵长类的光感受器我们会问： 1.视紫红质必须在其C末端区域被磷酸化 在体内正常关闭的催化活性？什么时候？ 发生了磷酸化吗？单个位点的磷酸化是否足以 导致完全关闭？ 2.arrestin是否必须与磷酸化视紫红质结合才能完全关闭？ Arrestin什么时候绑定？单单磷酸化能减少多少？ 催化活性？ 3.调节视紫红质的钙结合蛋白是否恢复素 关闭，使单光子响应可重现，调节增益 在背景光中发生的减少，还是两者都发生？ 4.视紫红质中的什么分子缺陷导致异常- 在正常灵长类杆状动物中发生的延长的单光子反应？是 年龄较大的视紫红质更有可能有缺陷？ 5.灵长类锥体细胞内钙的动态是什么，以及如何 它们是否与锥体闪光响应的双相波形有关？ 神经电路的实验将使用多电极阵列来 分离的灵长类视网膜神经节细胞的记录。我们会问： 6.神经节细胞群体的感受野是如何采样的 视觉图像？ 7.灵长类视网膜中的神经节细胞是否经历协同放电或 它们只发出独立的信号吗？如果出现协同射击，会发生什么？ 涉及信元，信号在多长范围内相关，以及 协同激发如何有助于检测对比度和 颜色呢？ 8.对神经节细胞感受野的贡献是什么 光感受器与水平细胞反馈之间的电耦合 在光感受器上？ 9.锥体本身是色泽适应的主要部位吗？ 视网膜，还是下游细胞参与其中？单锥体的适配性 类是否更改来自另一个锥类的信号的增益？

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?