Johns Hopkins scientists have created the most detailed 3D maps to date of oligodendrocytes—cells responsible for producing myelin—in the mouse brain. Using advanced 3D imaging, specialized microscopes, and artificial intelligence, the team mapped over 10 million oligodendrocytes across the entire brain, revealing precise locations and patterns of myelin distribution. The study, published online February 18 in Cell and funded by the National Institutes of Health, offers new insights into how myelin supports brain function and how its loss contributes to nervous system disorders. Oligodendrocytes wrap nerve cell axons in myelin, a fatty sheath that speeds up electrical signaling and supports long-term neural health. While myelin is abundant in white matter—the brain’s communication highways—this research shows oligodendrocytes are widespread throughout both white and gray matter, which contains most neurons and governs movement, memory, and sensory processing. The team, led by Dwight Bergles, Ph.D., at the Johns Hopkins University School of Medicine, developed a new imaging pipeline that combines tissue clearing—removing fats that block visibility—with light-sheet microscopy, enabling rapid, high-resolution scanning of entire brains. To identify and catalog millions of individual cells, they used machine learning algorithms trained to detect oligodendrocytes in complex images and reconstruct brain-wide maps. The maps capture oligodendrocyte distribution across the mouse lifespan, from two months to two years. The data show that while the total number of oligodendrocytes increases with age, the rate of addition varies significantly by brain region. Some areas added cells slowly and consistently over time, suggesting a tightly regulated developmental program. This stability may be disrupted by aging, injury, or disease, potentially contributing to neurological decline. The researchers found that brain regions receiving direct sensory input—such as those processing touch, sound, and vision—had three times more oligodendrocytes than areas like the primary motor cortex. This likely reflects the need for faster signal transmission in sensory processing. In experiments involving chemicals that destroy oligodendrocytes and myelin, the team identified regions particularly vulnerable and others more resilient. These differences may help explain why some brain areas are more affected in diseases like multiple sclerosis. In a mouse model of Alzheimer’s disease, the team discovered that myelin damage occurred not only near dense core amyloid-beta plaques—hallmarks of the disease—but also in white matter regions with diffuse plaques. This widespread vulnerability may help explain why oligodendrocyte dysfunction is common in Alzheimer’s, even in areas without visible plaques. The maps are publicly available for free, allowing other scientists to explore the data and accelerate research into brain development, aging, and disease. As Bergles notes, the work is like mapping a forest not just by where trees grow, but also by understanding the soil, climate, and geology—offering a comprehensive view of the brain’s ecosystem.