Title: Brain-wide delineation of myelin patterning on parvalbumin interneurons

Oligodendrocytes synthesize myelin, a specialized extension of membrane that wraps around axons. Myelin changes the electrical properties of the axonal segment it surrounds, resulting in the acceleration of action potential propagation that brain-wide alters the computational properties of neuronal networks. Myelin distribution varies dramatically between brain regions, neuronal types, and even within individual axons of the same neuron. Notably, myelin is far from a static structure: it gradually accumulates with age, can be modified by experience and learning, and can degenerate, leading to severe neurological impairments. Thus, elucidating how myelin is organized along different axons could improve our understanding of brain function in health and disease. However, current strategies for analyzing myelin patterning are low-throughput or have limited resolution. In this proposal, I will develop a new approach to study myelin distribution at the complete single-axon level across the adult mouse brain. By combining sparse genetic labeling in transgenic mice, high-resolution lightsheet microscopy, and AI-assisted computational methods, I will reconstruct the complete axonal trajectories of individual neurons in distinct brain regions and map the position of their myelin sheaths. This approach will enable the generation of robust myelin maps and reveal how myelin is organized across brain regions, neuronal types, and individual axons. Ultimately, the project will provide scalable tools for resolving myelin organization at unprecedented resolution in the brain.