Deep learning-based decoding of axonal ultrastructure in gene-edited mice using electron microscopy imaging

Abstract

Myelin forms an insulating sheath around axons enabling both rapid and energy-efficient conduction of action potentials and myelin abnormalities or loss can lead to severe motor, sensory, and cognitive impairment. While electron microscopy can resolve multiple axonal components that are affected myelin, their large-scale quantitative analysis is both difficult and time consuming. To overcome such limitations, we developed a machine learning framework that automatically recognizes and quantifies multiple features of axons and myelin including axonal mitochondrial density and periaxonal area. Applying that framework to fibers in the spinal cord of variably hypomyelinated mice, we show here that reduction in the thickness and length of myelin sheaths results in correlating changes in mitochondrial density and periaxonal area. The machine learning framework introduced here should contribute to future insight into the axon, myelin, and mitochondrial relationships that change during neurological plasticity and myelin disease progression.