Fig. 1

a Sample traces demonstrating EPSPs in hippocampal slices from control mice (left), demyelinated mice (middle, 12 weeks cuprizone), and remyelinated mice (right, 12 weeks cuprizone diet plus 6 weeks normal diet). EPSPs (arrows) present in myelinated slices were abolished by demyelination and restored by remyelination. Afferent Volley (AV) amplitude (asterisks) was similar in myelinated, demyelinated, and remyelinated slices. b High-frequency stimulation (HFS) (100 Hz stimulations 10 s apart) induced LTP in myelinated (Ctrl, top row) and remyelinated (Rem, bottom row) slices, but failed to induce LTP in demyelinated slices (Dem, middle row). Note multiple spikes (Rem, bottom trace) after LTP induction in remyelinated slices. c HFS stimulation induced comparable LTP in slices from myelinated (Control, black lines) and remyelinated slices (blue line). d Input–output plots indicated that HFS did not change excitability in remyelinated slices as AV amplitude remained the same across various stimulation intensity levels before and after HFS. e HFS induced LTP in remyelinated slices by potentiating synaptic transmission and increasing the slope of EPSPs. f Demyelination reduces hippocampal neuronal activity in vivo. Neuronal activity was measured in live mice using manganese-enhanced MRI. Four coronal MRI slices (the first is rostral, the fourth is caudal), in representative control (top row), demyelinated (middle row) and remyelinated (bottom row) mice, demonstrate differences in MnCl₂-enhanced hippocampi. The rightmost image for each row is a 3D representation of MnCl₂-enhancement in the hippocampus, with red voxels enhanced, and white voxels unenhanced. g Compared to myelinated hippocampi, MnCl₂-enhanced hippocampal volume was 54% lower in demyelinated hippocampi and 7% lower in remyelinated hippocampi. Hippocampal slice studies: n indicates slice numbers. Imaging studies: n = 10 mice for each group