GABAc Receptors & Mouse Retinal Ganglion Cell Responses

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DESCRIPTION (provided by applicant): Vision requires the integration of many aspects of the visual field into a cohesive whole that is used by the organism to navigate its environment. The mammalian retina is a laminar structure and each layer is populated by several cell types that combine to define the response properties of the retinal ganglion cells (RGCs), which transmit the signal to the brain. The many aspects of the visual scene are encoded by two parallel pathways within the retina that either detect increases or decreases in light intensity. There are many types of RGCs and their responses are defined by the inputs they receive. One key element in shaping their response properties is inhibition, which like other regions of the brain is mediated by glycine and gamma amino butyric acid (GABA). GABA inhibition is mediated by three receptors, GABAA, GABAB and GABAC, all of which are present in the retina. One challenge then is to determine how each of these inhibitory and excitatory inputs shapes the responses of the RGCs. A new tool towards attaining this goal is the ability to manipulate the mouse genome and selectively remove specific inputs, the effect of which then can be assessed on the RGCs. However, unlike the extensive literature for cat, rabbit and primate, relatively little is known about the fundamental properties of murine RGCs. The goal of this proposal is to characterize the response properties of mouse RGCs both in vivo and in vitro, and in particular determine the role that GABACR-mediated input plays in shaping the responses. The specific aims are (1) to determine the effect of eliminating, genetically, GABACR-mediated inhibition on a subset of RGC response properties recorded in vivo, and (2) correlate structure and function of a diverse set of RGCs, and determine the impact of eliminating GABACR-mediated input on the response properties of each of these cell types. These data will enhance our understanding of the role of inhibition in shaping the response of the output cells of the retina, and therefore important aspects of integration of information in the visual field.