Neuronal Silencing and Protection in a Mouse Model of Demyelination

Damage to the myelin sheath that protects axons in the central nervous system is a hallmark pathology of demyelinating diseases like multiple sclerosis. Cuprizone-induced demyelination in mice is a common model for studying demyelination and remyelination. However, the relationship between myelin damage and recovery and neuronal function remains poorly understood. By monitoring hippocampal myelination and neuronal activity in the same mice, we assessed longitudinal changes following cuprizone consumption and remyelination treatment. Upon cuprizone consumption, a rapid decline in neuronal activity preceded slower demyelination. Female mice showed a more intense early decrease in brain activity and a stronger correlation with levels of myelin loss. Remyelination treatment led to increased myelination levels and recovery of neuronal activity compared to vehicle treatment. Changes in single-neuron firing rates during treatment were proportional to the pre-cuprizone firing rate in the same cells, highlighting a potential linkage between the status of myelin recovery and cellular activity.