PT - JOURNAL ARTICLE AU - Laura Hanson AU - Santhosh Sethuramanujam AU - Geoff deRosenroll AU - Gautam B. Awatramani TI - Retinal direction selectivity in the absence of asymmetric starburst amacrine cell responses AID - 10.1101/428532 DP - 2018 Jan 01 TA - bioRxiv PG - 428532 4099 - http://biorxiv.org/content/early/2018/09/26/428532.short 4100 - http://biorxiv.org/content/early/2018/09/26/428532.full AB - In the mammalian retina, asymmetric inhibitory signals arising from the direction-selective dendrites of GABAergic/cholinergic starburst amacrine cells are thought to be crucial for originating direction selectivity. Contrary to this notion, however, we found that direction selectivity in downstream ganglion cells remains remarkably unaffected when starburst output is rendered non-directional (using a novel strategy combining a conditional GABAA α2 receptor knockout mouse with optogenetics). We show that temporal asymmetries between excitation/inhibition, arising from the differential connectivity patterns of starburst cholinergic and GABAergic synapses to ganglion cells, form the basis for a parallel mechanism generating direction selectivity. We further demonstrate that these distinct mechanisms work in a coordinated way to refine direction selectivity as the stimulus crosses the ganglion cell’s receptive field. Thus, precise spatiotemporal patterns of inhibition and excitation that shape directional responses in ganglion cells are shaped by two ‘core’ mechanisms, both arising from distinct specializations of the starburst network.