Adaptive Neural control of Respiration in Drosophila

Energy-intensive behaviors demand high oxygen supply, presenting a fundamental physiological challenge across the animal kingdom. Respiratory organs have evolved diverse forms - from insect spiracles to fish gills to human lungs. Yet their neural control systems serve a conserved purpose. They need to actively monitor respiratory gases and regulate both gas exchange and energy consumption during behavior. The neural mechanisms coordinating respiration with behavior remain poorly understood. In particular, we know little about how respiratory circuits interact with motor control systems during varying metabolic demands. Here I propose to investigate the neural basis of respiratory control during behavior. I have made two important discoveries that uniquely position me to investigate the neural control of respiration. I have identified the complete set of motor neurons controlling respiration in flies, and I have discovered novel gas- sensing neurons in muscles and respiratory tracts that detect respiratory state and modulate behavior. I have made genetic drivers that label both populations of neurons. With these advantages, I will investigate three fundamental aspects of respiratory control by combining genetics, connectomics, behavioral tracking, and in vivo imaging. First, I will examine the neuromuscular basis of respiratory control during locomotion. Second, I will investigate interoceptive mechanisms of respiratory gas sensing. Third, I will study the neural integration of respiratory and metabolic signals. This work will reveal how animals optimize respiratory control while maintaining homeostasis during behavior. The principles uncovered in this tractable system will provide an experimental and conceptual framework for studying respiratory control across species. My long-term goal is to establish an independent research program on neural control of respiration and energy homeostasis. The research and career development in this proposal will provide essential experimental, theoretical, and mentorship training. To support my transition to independence, I will be co-mentored by two experts at the University of Washington: Dr. John Tuthill, an expert on sensorimotor control in flies, and Dr. Jan-Marino Ramirez, an expert on mammalian respiratory control. Project Number: 1K99NS146574-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Neurological Disorders and Stroke (NINDS) | Principal Investigator: Yichen Luo | Institution: UNIVERSITY OF WASHINGTON, SEATTLE, WA | Award Amount: $122,769 | Activity Code: K99 | Study Section: Special Emphasis Panel[ZRG1 ICN-T (94)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11281168