I(h) Channels Control Feedback Regulation from Amacrine Cells to Photoreceptors

In both vertebrates and invertebrates, photoreceptors’ output is regulated by feedback signals from interneurons that contribute to several important visual functions. Although synaptic feedback regulation of photoreceptors is known to occur in Drosophila, many questions about the underlying molecular mechanisms and physiological implementation remain unclear. Here, we systematically investigated these questions using a broad range of experimental methods. We isolated two I(h) mutant fly lines that exhibit rhythmic photoreceptor depolarization without light stimulation. We discovered that I(h) channels regulate glutamate release from amacrine cells by modulating calcium channel activity. Moreover, we showed that the eye-enriched kainate receptor (EKAR) is expressed in photoreceptors and receives the glutamate signal released from amacrine cells. Finally, we presented evidence that amacrine cell feedback regulation helps maintain light sensitivity in ambient light. Our findings suggest plausible molecular underpinnings and physiological effects of feedback regulation from amacrine cells to photoreceptors. These results provide new mechanistic insight into how synaptic feedback regulation can participate in network processing by modulating neural information transfer and circuit excitability.