Understanding signal processing in retinal bipolar cell pathways

点击翻译按钮获取中文摘要

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.