Project Summary [30 lines max] Timing is critical to neural processing. Nowhere is that clearer than in visual motion detection. To detect motion, neurons transmit visual information with different latencies, or delays, allowing the circuit to compare visual scenes over time. When comparisons over time are combined with comparisons over space, the circuit can compute direction-selective signals, which are larger for motion in one direction than in the opposite direction. These signals in turn guide a wide range of behaviors, from navigation and predator avoidance to mating. This project proposes to investigate the origins and effects of timing differences in visual motion circuits in the fruit fly Drosophila, a model organism in which powerful genetic tools can identify the roles of individual neurons in computations. Using these tools, this research will identify mechanisms that underlie the different dynamical responses of visual neurons and map out how those responses control downstream computations. This work is significant for two reasons. First, motion detection is a canonical neural computation, since it requires circuits to integrate visual information over both time and space, and because it is necessarily nonlinear. Moreover, the anatomy, physiology, and computational structure of motion detection has strong parallels between flies and mammalian retina and cortex. Therefore, it is likely that what we learn about the mechanisms that regulate timing the fly eye and their effects on motion computation will be mirrored in other circuits that detect visual motion. Second, our proposed aims will test fundamental models of motion detection. All of these models rely on timing differences that permit comparisons to be made over time, but these assumptions have not been tested. Our research will distinguish between proposed models in the fly and test fundamental assumptions about how motion is computed by differences in the timing of neural signals. In our complementary aims, we will uncover mechanisms that generate different timing in different neural responses. We will also measure the effects of timing differences on motion signals and on behavior. On completion, these studies will advance our understanding of how neural response timing is regulated and how that timing determines downstream neural computations. We expect that what we learn in this small neural circuit can serve as a scaffold for understanding the roles of timing in motion detection in the larger brains of mammals.