Longitudinal in vivo monitoring of axonal degeneration after brain injury

Traumatic brain injury (TBI)-induced axonal degeneration leads to acute and chronic neuropsychiatric impairment, neuronal death, and accelerated neurodegenerative diseases of aging, including Alzheimer’s and Parkinson’s diseases. In laboratory models, axonal degeneration is traditionally studied through comprehensive postmortem histological evaluation of axonal integrity at multiple time points. This requires large numbers of animals to power for statistical significance. Here, we developed a method to longitudinally monitor axonal functional activity before and after injury in vivo in the same animal over an extended period. Specifically, after expressing an axonal-targeting genetically encoded calcium indicator in the mouse dorsolateral geniculate nucleus, we recorded axonal activity patterns in the visual cortex in response to visual stimulation. In vivo aberrant axonal activity patterns after TBI were detectable from 3 days after injury and persisted chronically. This method generates longitudinal same-animal data that substantially reduces the number of required animals for preclinical studies of axonal degeneration.