This application proposes to study mechanisms of synaptic integration by cholinergic (starburst) amacrine and direction-selective ganglion cells (DSGCs) in the mature rabbit retina with an overall goal to elucidate synaptic and cellular mechanisms underlying complex visual processing in the inner mammalian retina, particularly the detection of motion direction. The proposed studies are based on recent findings of several labs, including ours, that strongly suggest a critical role of starburst cells in the generation of direction selectivity (DS). These studies moved the key unknown issues regarding DS mechanisms to sites upstream of DSGCs and raised some fundamental questions that require a new level experimentation to answer. Here we identify 3 specific aims that will test 2 central hypotheses about the mechanisms underlying the synaptic, cellular, and network functions of starburst cells: 1) to determine the mechanisms of synaptic interaction among starburst cells, 2) to determine the synaptic mechanism of direction-selective light responses in starburst distal processes, 3) to determine the mechanisms of synaptic interaction between starburst and ganglion cells. We will use a powerful wholemount rabbit retinal preparation, which allows the integration of dual patch-clamp recording from starburst cells and DS ganglion cells, simultaneous flash photolysis (UV uncaging) and dual patch clamp, and simultaneous calcium imaging, patch clamp, and light stimulation. The ability to apply these cutting-edge techniques to a living mammalian retina will enable us to gather critical information previously unattainable in other experimental settings. Our experimental approach is unique in that it will directly and systematically measure synaptic interactions among key components of the DS circuit and it will use detailed synaptic physiology to explain the light response properties recorded from the same identified neurons.
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