Understanding signal processing in retinal bipolar cell pathways

我们开发了一个强大的小鼠模型来研究平行视网膜双极细胞的信息处理 小路。双极细胞是将光感受器输出传输到神经节细胞所必需的，神经节细胞 将视觉信息发送到大脑中的一系列目标区域。双极细胞分为大约12种类型 并构成视觉系统中信息处理的第一级。虽然双极的几个方面 细胞功能已经在各种物种的视网膜切片制备中得到了解决，关于 双极细胞信号的三个基本方面仍然缺乏。首先是简明扼要的定量描述。 任何基因识别的双极细胞类型的时空感受野。第二个是一个 控制每个BC的输入-输出传递函数的神经机制的综合说明 类型，基于具有完整电路的光诱发反应(整装视网膜准备)。三是 光适应机制对双极细胞视觉功能的影响。 我们将利用我们最近开发的活细胞成像和全细胞记录方法来 解决这些问题。具体地说，我们将在转基因小鼠的整体视网膜中进行有针对性的电生理记录，这些小鼠带有基因识别的双极细胞；我们将使用双光子荧光 转基因小鼠体内钙和谷氨酸的基因编码荧光生物传感器成像 非双极通路的功能缺失突变；我们将使用高级视觉刺激 方法从双极细胞水平阐明光适应的机制。这些研究将提供 关于双极细胞如何编码视觉信息以及视觉敏感性如何的有价值的信息 在不同的刺激条件下维持。了解已识别视网膜的信息处理 信号通路对发育和神经系统疾病的研究和潜在治疗至关重要。 疾病，以及视网膜疾病。

We have developed a powerful mouse model to study information processing in parallel retinal bipolar cell pathways. Bipolar cells are essential for transmitting the photoreceptor output to the ganglion cells, which signal visual information to a range of target areas in the brain. Bipolar cells divide into about a dozen types and constitute the first level of information processing in the visual system. While several aspects of bipolar cell function have been addressed in retinal slice preparations of a variety of species, information about three fundamental aspects of bipolar cell signaling is still lacking. First is a concise, quantitative description of the spatio-temporal receptive field for any genetically identified bipolar cell type. Second is a comprehensive account of the neural mechanisms that govern the input-output transfer function of each BC type, based on light-evoked responses with intact circuitry (whole-mount retina preparation). Third is the impact of light-adaptive mechanisms on bipolar cell visual function. We will leverage our recently developed live-cell imaging and whole-cell recording methods to address these issues. Specifically, we will make targeted electrophysiological recordings in the whole-mount retina of transgenic mice with genetically identified bipolar cells; we will use two-photon fluorescence imaging with genetically encoded fluorescent biosensors for calcium and glutamate in transgenic mice with loss-of function mutations in the OFF bipolar pathways; and we will use advanced visual stimulation methods to elucidate mechanisms of light-adaptation at the bipolar cell level. These studies will provide valuable information about how bipolar cells encode visual information, and how visual sensitivity is maintained under varying stimulus conditions. Understanding information processing in identified retinal signaling pathways is critical for the study and potential treatment of developmental and neurological disorders, and retinal disease.