Cuprizone-induced demyelination provokes abnormal intrinsic properties and excitatory synaptic transmission in the male mouse anterior cingulate cortex.

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS). Demyelination in the CNS provokes hyperalgesia, negative emotions, and/or cognitive impairment. Cuprizone (CPZ)-induced demyelination is a major demyelinating disease model for rodents. The anterior cingulate cortex (ACC) is a brain region that is responsible for higher brain functions related to MS symptoms. However, little is known whether CPZ exposure induces demyelination in the ACC coincides with changes to intrinsic neuron properties and synaptic transmission. In this study, we first examined if CPZ exposure induces demyelination in the male mouse ACC. CPZ exposure induced demyelination in the ACC and decreased body weight. In addition, demyelination altered intrinsic properties and excitatory synaptic transmission in layer II/III pyramidal neurons from the ACC as indicated by whole-cell patch-clamp in brain slice preparations. CPZ exposure decreased the frequency of action potentials due to increasing rheobase. At the synapse level, CPZ exposure also suppressed evoked excitatory synaptic transmission to the ACC. Finally, CPZ exposure also changed the kinetics of AMPA and NMDA receptors. These results suggest that CPZ exposure induces demyelination in the ACC coinciding with changes in intrinsic properties, action potentials and excitatory synaptic transmission.