All-optical interrogation of a direction selective retinal circuit by holographic wave front shaping

Direction selective (DS) ganglion cells (GC) in the retina maintain their tuning across a broad range of light levels. Yet very different circuits can shape their responses from bright to dim light, and their respective contributions are difficult to tease apart. In particular, the contribution of the rod bipolar cell (RBC) primary pathway, a key player in dim light, is unclear. To understand its contribution to DSGC response, we designed an all-optical approach allowing precise manipulation of single retinal neurons. Our system activates single cells in the bipolar cell (BC) layer by two-photon (2P) temporally focused holographic illumination, while recording the activity in the ganglion cell layer by 2P Ca 2 imaging. By doing so, we demonstrate that RBCs provide an asymmetric input to DSGCs, suggesting they contribute to their direction selectivity. Our results suggest that every circuit providing an input to direction selective cells can generate direction selectivity by itself. This hints at a general principle to achieve robust selectivity in sensory areas.