Wilson, Rachel IZhang, Wenyi2026-06-0920262026-06-052026Zhang, Wenyi. 2026. Mechanisms of Setpoint Control in Drosophila Navigation System. Doctoral Dissertation, Harvard University Graduate School of Arts and Sciences.32701082https://dash.harvard.edu/handle/1/42740316Navigation provides a useful framework for studying how animals balance behavioral persistence with flexibility. Animals often maintain internal setpoints that stabilize behavior, but these setpoints must remain adjustable as external conditions change. In Drosophila, stable heading can support persistent navigation, whereas sensory stimuli can redirect locomotion away from an established course. The neural mechanisms that allow such flexible setpoint control remain poorly understood. Here we identify hΔA, a central-complex cell type involved in this process. In a heat paradigm, hΔA was required for sensory-driven deviation from a persistent goal direction. hΔA population activity contained two separable components: a sinusoidal bump and a spatially uniform signal. The bump component was inherited from the travel-direction input hΔB and encoded a slowly varying travel-direction signal consistent with a short-timescale setpoint. Optogenetic stimulation showed that this activity was sufficient to bias steering. The uniform component, by contrast, increased with turning and at heat onset. We further identified FB5V as a modulatory input to hΔA that contributes to this signal. FB5V activity was spatially uniform, scaled with rotational speed, and provided direct excitatory input to hΔA. These properties suggest that FB5V may act as an exploratory drive that promotes sampling of different headings before a new direction is stabilized. Together, these findings support a model in which short- and long-timescale setpoints compete for steering control, and suggest a circuit mechanism by which flies balance directional persistence with flexible reorientation under changing sensory conditions.application/pdfenfeedback controlmotor circuitnavigationNeurosciencesThesis or Dissertation2026-06-090000-0002-0132-9794