A Spinal Circuit for Hypoxia-Evoked Motor Output in Zebrafish Larvae

Abstract

Oxygen availability is a critical environmental variable that shapes animal physiology and behavior. In larval zebrafish, acute hypoxia elicits a distinct increase in rhythmic pectoral fin movements, a behavior thought to facilitate oxygen uptake. While peripheral oxygen sensors such as neuroepithelial cells (NECs) and Merkel-like cells (MLCs) have been well characterized, the motor circuits responsible for executing this behavior remain unknown. Four distinct lower motor nerve branches in the spinal cord have been shown to innervate the pectoral fin muscles and are candidate effectors of hypoxia-induced behaviors. Here, we identify the neural pathways that transform hypoxia detection into a dedicated motor output. Using high-speed behavioral tracking, we confirm that hypoxia reliably increases pectoral fin beat frequency without affecting locomotor tail activity or visually guided swimming. Two-photon calcium imaging in Tg(ChaTa:Gal4;UAS:GCaMP6s) larvae reveals that a subset of cholinergic spinal motor neurons is selectively active during hypoxia-induced fin movements. Targeted laser ablation of pectoral fin motor nerves abolishes the response, demonstrating the necessity of descending input for this behavior. Our findings define a distributed, partially redundant motor circuit that implements a homeostatic fin response to hypoxia. By establishing a mechanistic framework for this behavior in a genetically accessible vertebrate model, this work enables future studies of oxygen sensing, sensorimotor integration, and the neural basis of homeostatic motor control.