Cellular mechanisms for integral feedback in visually guided behavior

Significance Visually driven behaviors of Drosophila have become a model system to study how neural circuits process sensory information. Here, we show that one of the computations performed by this system is temporal integration of visual motion. We provide evidence of how this computation might be performed by measuring the activity of identified visual interneurons during tethered flight that are thought to control the described behavior: Presynaptic calcium accumulation in these neurons mimics a leaky temporal integration of the visual motion signal as does the behavior. In the future, the genetic tools available in Drosophila will enable studying the precise mechanism of temporal integration in this model system, which could provide insights into general mechanisms of neuronal information processing. Sensory feedback is a ubiquitous feature of guidance systems in both animals and engineered vehicles. For example, a common strategy for moving along a straight path is to turn such that the measured rate of rotation is zero. This task can be accomplished by using a feedback signal that is proportional to the instantaneous value of the measured sensory signal. In such a system, the addition of an integral term depending on past values of the sensory input is needed to eliminate steady-state error [proportional-integral (PI) control]. However, the means by which nervous systems implement such a computation are poorly understood. Here, we show that the optomotor responses of flying Drosophila follow a time course consistent with temporal integration of horizontal motion input. To investigate the cellular basis of this effect, we performed whole-cell patch-clamp recordings from the set of identified visual interneurons [horizontal system (HS) cells] thought to control this reflex during tethered flight. At high stimulus speeds, HS cells exhibit steady-state responses during flight that are absent during quiescence, a state-dependent difference in physiology that is explained by changes in their presynaptic inputs. However, even during flight, the membrane potential of the large-field interneurons exhibits no evidence for integration that could explain the behavioral responses. However, using a genetically encoded indicator, we found that calcium accumulates in the terminals of the interneurons along a time course consistent with the behavior and propose that this accumulation provides a mechanism for temporal integration of sensory feedback consistent with PI control.