Visual information in the mammalian retina is segregated into functionally and anatomically specialized channels for parallel processing. The mouse retina contains approximately ~40 retinal ganglion cell (RGC) types. Each type can be distinguished based on the spatiotemporal properties of their light responses and their distinctive morphological features. The RGC types each perform complex neural computations to convey specific aspects of the visual scene to retino-recipient areas of the brain. These complex computations arise from an interplay between excitatory and inhibitory signals centered on the dendrites of individual RGC types. These computations remain largely unresolved due to our lack of knowledge of the roles played by a diverse class inhibitory interneurons, the amacrine cells (ACs). The purpose of this study is to characterize the response properties, functional connections, and visual processing roles of a newly discovered amacrine cell, the CK2-AC1. This project uses powerful intersectional strategies available in the mouse retina. Specifically, a CaMk2a-tTA driver line is crossed with a tamoxifen inducible Slc32a1-iCreER driver line to exclusively label CK2-AC1 cells. The response properties of CK2-AC1 are probed by genetically labeling with GCaMP6f, ChR2, and DREADDS. 2- photon imaging is used to record dendritic Ca2+ signals to measure receptive field properties and determine feature selectivity mechanisms. The results show that CK2-AC1 is a glycinergic OFF center cell that is both orientation (OS) and object-motion sensitive (OMS). Experiments with ChR2 mapping revealed that CK2-AC1s provide glycinergic inhibition to a type of ON-OFF orientation selective RGC named HD1-RGC along with several other types of RGCs (HD2, F-minioff, and G4). Finally, the functional roles of CK2-AC1 in visual processing were examined by using DREADDs to reversibly to reversibly silence activity. CK2-AC1 provided both orthogonal and OMS suppression to HD1- and HD2-RGCs. These findings indicate that CK2-AC1 is a multi-tasking AC that confers orientation selectivity and object motion sensitivity on different RGC types. This work will enhance our understanding of specific retinal circuits and will provide a general template for a genetic dissection of inner retinal circuits.
The overall goal of my research is to understand visual processing in the inner retina. This study will provide new insights for next generation retinal prosthetics and help design better therapeutic strategies for pathophysiological neuronal mechanisms of retinal diseases.
