TY - JOUR T1 - Parallel Synaptic Acetylcholine Signals Facilitate Large Monopolar Cell Repolarization and Modulate Visual Behavior in <em>Drosophila</em> JF - The Journal of Neuroscience JO - J. Neurosci. SP - 2164 LP - 2176 DO - 10.1523/JNEUROSCI.2388-20.2021 VL - 41 IS - 10 AU - Jinglin Wu AU - Xiaoxiao Ji AU - Qiuxiang Gu AU - Buxin Liao AU - Wei Dong AU - Junhai Han Y1 - 2021/03/10 UR - http://www.jneurosci.org/content/41/10/2164.abstract N2 - Appropriate termination of the photoresponse in image-forming photoreceptors and downstream neurons is critical for an animal to achieve high temporal resolution. Although the cellular and molecular mechanisms of termination in image-forming photoreceptors have been extensively studied in Drosophila, the underlying mechanism of termination in their downstream large monopolar cells remains less explored. Here, we show that synaptic ACh signaling, from both amacrine cells (ACs) and L4 neurons, facilitates the rapid repolarization of L1 and L2 neurons. Intracellular recordings in female flies show that blocking synaptic ACh output from either ACs or L4 neurons leads to slow repolarization of L1 and L2 neurons. Genetic and electrophysiological studies in both male and female flies determine that L2 neurons express ACh receptors and directly receive ACh signaling. Moreover, our results demonstrate that synaptic ACh signaling from both ACs and L4 neurons simultaneously facilitates ERG termination. Finally, visual behavior studies in both male and female flies show that synaptic ACh signaling, from either ACs or L4 neurons to L2 neurons, is essential for the optomotor response of the flies in high-frequency light stimulation. Our study identifies parallel synaptic ACh signaling for repolarization of L1 and L2 neurons and demonstrates that synaptic ACh signaling facilitates L1 and L2 neuron repolarization to maintain the optomotor response of the fly on high-frequency light stimulation.SIGNIFICANCE STATEMENT The image-forming photoreceptor downstream neurons receive multiple synaptic inputs from image-forming photoreceptors and various types of interneurons. It remains largely unknown how these synaptic inputs modulate the neural activity and function of image-forming photoreceptor downstream neurons. We show that parallel synaptic ACh signaling from both amacrine cells and L4 neurons facilitates rapid repolarization of large monopolar cells in Drosophila and maintains the optomotor response of the fly on high-frequency light stimulation. This work is one of the first reports showing how parallel synaptic signaling modulates the activity of large monopolar cells and motion vision simultaneously. ER -