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.

Public Health Relevance

Vision critically depends on the transmission of visual information from the photoreceptors in the retina to central visual areas in the brain. Space limitations within the optic nerve, in particular, prevent individual photoreceptor cells to contact central areas in the brain directly. Instead, the photoreceptor output is integrated and processed by neural circuits within the retina, to generate a more compact representation of the visual image for transmission to the brain. The goal of this proposal is to further our understanding of a critical information-processing step within the retina that is performed by the retinal bipolar cells. In a series of innovative experiments we will measure and compare information processing properties across bipolar cells types, identify the neural mechanisms that give rise to their unique visual encoding, and study how stimulus conditions impact bipolar cell function. Understanding information processing in retinal bipolar cells is an essential prerequisite for understanding the neural circuit functions that need to be reestablished through regenerating and restoring neuronal connections during retinal disease and aging, an `audacious goal' established by the NEI.

National Institute of Health (NIH)
National Eye Institute (NEI)
Research Project (R01)
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Neurotransporters, Receptors, and Calcium Signaling Study Section (NTRC)
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Greenwell, Thomas
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University of Louisville
Anatomy/Cell Biology
Schools of Medicine
United States
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Borghuis, Bart G; Ratliff, Charles P; Smith, Robert G (2018) Impact of light-adaptive mechanisms on mammalian retinal visual encoding at high light levels. J Neurophysiol 119:1437-1449