The tectal melanocortin system modulates energy-dependent visual avoidance behavior in zebrafish

Summary Energy homeostasis depends on both food intake and behavioral control of energy expenditure. The hypothalamic melanocortin system is classically associated with feeding regulation, but its broader behavioral roles remain less defined. Using larval zebrafish, we show that hypothalamic pro-opiomelanocortin (pomca)-expressing neurons project to the tectum and target neurons expressing the melanocortin receptor Mc4r. Rather than altering prey consumption, melanocortin signaling in this circuit modulates visually guided avoidance of small stimuli, an energy-demanding behavior. Sated larvae, with higher energy reserves, avoid small objects (prey or other, potentially harmful, protozoa) more readily, while hungry larvae do not. Importantly, disrupting Mc4r signaling in sated fish reduces this avoidance behavior, indicating that the melanocortin system gates energy expenditure decisions based on internal state. These findings uncover a previously undescribed function for hypothalamic melanocortin signaling in tuning sensorimotor responses to visual stimuli, not to regulate feeding per se but to modulate behavioral energy allocation.