GABAergic Inhibition Controls Receptive Field Size, Sensitivity, and Contrast Preference of Direction Selective Retinal Ganglion Cells Near the Threshold of Vision

Information about motion is encoded by direction -selective retinal ganglion cells (DSGCs). These cells reliably transmit this information across a broad range of light levels, spanning moonlight to sunlight. Previous work indicates that adaptation to low light levels causes heterogeneous changes to the direction tuning of ON - OFF (oo)DSGCs and suggests that superior -preferring ON - OFF DSGCs (s-DSGCs) are biased toward detecting stimuli rather than precisely signaling direction. Using a large-scale multielectrode array, we measured the absolute sensitivity of ooDSGCs and found that s-DSGCs are 10 -fold more sensitive to dim fl ashes of light than other ooDSGCs. We measured their receptive fi eld (RF) sizes and found that s-DSGCs also have larger receptive fi elds than other ooDSGCs; however, the size difference does not fully explain the sensitivity difference. Using a conditional knock -out of gap junctions and pharmacological manipulations, we demonstrate that GABA-mediated inhibition contributes to the difference in absolute sensitivity and receptive fi eld size at low light levels, while the connexin36-mediated gap junction coupling plays a minor role. We further show that under scotopic conditions, ooDSGCs exhibit only an ON response, but pharmacologically removing GABA-mediated inhibition unmasks an OFF response. These results reveal that GABAergic inhibition controls and differentially modulates the responses of ooDSGCs under scotopic conditions.