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Intersectional genetic dissection of Inner retinal circuits

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Different features of the visual world are conveyed to the retino-recipient regions of the brain by more than 40 types of retinal ganglion cells (RGCS). Feature detection by RGCs depends on a combination of intrinsic and morphological properties where the interplay of excitatory and inhibitory inputs occurs through local retinal circuits. RGC feature selectivity is modulated/shaped through a class of inhibitory retinal interneurons called amacrine cells (ACs). ACs are the most diverse neuronal cell type in the vertebrate retina. Despite significant advances in both genetic and optical techniques little is still known about the contribution of ACs to visual processing and retinal disease. Through Cre/tTA intersectional genetics, we have identified two new narrow field AC types in the mouse retina called SIAC and CK2-AC1. We characterized their genetic and functional properties and circuit roles with single cell RNA sequencing (scRNA-seq), GCaMP and iGluSnFr optical imaging, and electrophysiological recordings. We found that SIAC exhibits unconventional light responses created by a sign-inverting glutamatergic synapse meditated by mGlur8 activation following release from ON bipolar cells. In addition, we discovered CK2-AC1 is object motion sensitive (OMS) and, together with other ACs, controls the OMS signals that RGCs send to the brain. Overall, we report several new and unconventional AC processing mechanisms and offer novel insights into how ACs contribute to visual processing in the mammalian retina.

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