Investigating the Role of Descending Neurons in Freely Flying <em>Drosophila melanogaster</em>

Abstract

Understanding how neural circuits generate complex behaviors remains a central challenge in neuroscience. This thesis investigates the neural basis of flight control in <em>Drosophila melanogaster</em>, focusing on how descending neurons (DNs) control rapid turning maneuvers known as saccades during free flight. Saccades are stereotyped turning behaviors that allow flies to quickly reorient their flight direction, occurring either spontaneously during exploration or in response to visual threats such as looming stimuli, which signal approaching predators. Descending neurons form the critical link between the brain and motor circuits in the ventral nerve cord, transmitting commands that coordinate these flight maneuvers. Through the development of an experimental system integrating real-time three-dimensional tracking with closed-loop optogenetic manipulation, I examined the functional roles of specific DNs in controlling flight behavior. <br/> Behavioral analysis revealed distinct kinematic signatures between spontaneous exploratory saccades and looming-evoked escape saccades, indicating context-dependent control mechanisms. Optogenetic activation and genetic silencing experiments demonstrated that individual DNs contribute differentially to flight maneuvers: DNa15 primarily influenced spontaneous turning behaviors, while DNp03 specifically affected escape responses to visual threats. This functional separation suggests the existence of parallel pathways that are selectively recruited based on behavioral context. <br/> The results suggest that flight control emerges from functionally specialized, but interacting neural pathways rather than through uniform activation of descending circuits. While individual DN activation can influence flight trajectories, the persistence of saccadic behaviors following targeted silencing indicates that motor control involves distributed processing across multiple descending pathways.