Molecular identification of wide-field amacrine cells in mouse retina that encode stimulus orientation

Visual information processing in the retina is sculpted by a diverse group of inhibitory interneurons called amacrine cells. For most of the >60 amacrine cell types, molecular identities and specialized functional attributes remain unknown. Here, we developed an intersectional genetic strategy to target a group of wide-field amacrine cells (WACs) in mouse retina that co-express the transcription factor Bhlhe22 and the Kappa Opioid Receptor (KOR; B/K WACs). B/K WACs feature straight, unbranched dendrites spanning over 0.5 mm (~15 deg visual angle) and produce non-spiking responses to either light increments or decrements. Two-photon dendritic population imaging reveals Ca2+ signals tuned to the physical orientations of B/K WAC dendrites, signifying a robust structure-function alignment. B/K WACs establish divergent connections with multiple retinal neurons, including unexpected connections with non-orientation-tuned ganglion cells and bipolar cells. Our work sets the stage for future comprehensive investigations of the most enigmatic group of retinal neurons: WACs.