Rod photoreceptors control the ON vs OFF polarity of cone-signaling neurons

A fundamental feature of the visual system is its ability to detect image contrast. The contrast processing starts in the first synapse of the retina where parallel pathways are established to compute contrast to bright (ON pathway) and dark (OFF pathway) objects, separately transferred to morphologically identified ON and OFF cells throughout the visual system. Here, we found that response polarity in ON and OFF neurons is not fixed but rather switches dynamically to the opposite polarity. The switch was not observed in rod-knockout mice, indicating that rods generate the polarity switch. We determined that neither horizontal cells nor rod-signaling pathways were responsible for the switch. Instead, we discovered that EAAT5 glutamate transporters located at photoreceptor terminals were required to produce the polarity switch. Our findings exhibit the plasticity of ON-OFF coding in retinal interneurons and their ability to encode contrast across the visual dynamic range. Rod and cone signaling interactions via glutamate spillover are identified as mechanisms underlying ON and OFF light response polarity switches in retinal interneurons.