Signal Processing in the Inner Retina

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The mammalian retina contains at least 40 types of retinal ganglion cells (RGCs) each tuned to respond best to different and sometimes complex features in a visual scene. Together, these diverse RGC responses provide us with all of the information that we use to navigate in the visual world. Each type of RGC monitors a patch on the retinal surface, its receptive field, by collecting inputs from presynaptic bipolar and amacrine cells of which there are more than 12 and 50 types, respectively. While the general patterns of amacrine and bipolar cell connectivity that contribute to RGC light responses are known, the daunting complexity of the inner synaptic layer of the retina has impeded our understanding of the connections that underlie the tuning properties that distinguish the RGC types. Specifically, there is currently no systematic way to identify all of the cells that make presynaptic inputs to an RGC and at the same time study their combined function as a processing unit. This proposal uses a toolbox of viral techniques to trace and functionally characterize the amacrine and bipolar cells that provide input to specific RGCs in both the rod dominant mouse and cone dominant ground squirrel retinas. In three specific aims, our goals are to: 1) use a trans-synaptic rabies virus that expresses GFP to map the direct bipolar and amacrine cell inputs to genetically targeted RGCs in the mouse retina; 2) use a trans-synaptic rabies virus that expresses the Ca2+ indicator protein GCaMP6 to study the functional connections between RGCs and their direct inputs from bipolar and amacrine cells in the mouse retina; and, 3) identify and functionally characterize the inner retinal circuits responsible for blue/green color opponent vision in the ground squirrel. Our work will define the wiring and functions of specific inner retinal circuits in health and provide the background for understanding circuit changes that are known to occur following photoreceptor degeneration, whether from genetic or age-onset disease.