Kavli Affiliate: Aniruddha Das
| Authors: Aniruddha Das, Julie Borovicka, Hale Tobin, Shruti Bhatia, Jacob Icardi, Ghazaal Tahmasebi, Priyanka Agochiya, Shriya Singh, Bruce Trapp and Hod Dana
| Summary:
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 the functional properties of ensheathed neurons remains poorly understood. Using concurrent monitoring of hippocampal myelination and neuronal firing rates in the same mouse, we assessed longitudinal changes during cuprizone consumption and remyelination treatment. The data revealed a rapid decline in neuronal activity that preceded myelin loss. Females showed a more severe decrease after 4 days of cuprizone, which correlated with enhanced neuronal activity and myelin loss 51 days later, whereas male mice showed a more severe decline in neuronal activity after 55 days of cuprizone. Following cuprizone cessation, mice were treated with Clemastine or vehicle for 45 days. A short-term recovery was found in both groups, before the Clemastine group showed increased remyelination and higher neuronal firing rates. The mean increase and decrease in firing rates were proportional to the same-neuron baseline firing rate in the Clemastine and vehicle groups, respectively, highlighting a potential linkage between the status of myelin recovery and cellular activity.