Focal cortical dysplasia (FCD) is a regional malformation of cortical development frequently associated with pharmacoresistant epilepsy. It is caused by somatic mutations affecting the mTOR signaling pathway within excitatory neurons. At the cellular level, FCD manifests as the emergence of dysmorphic neurons, disrupted neuronal migration, and consequent alterations in neuronal circuitry, accompanied by seizure occurrence. It has been demonstrated that physiological neuronal activity stimulates oligodendrocyte lineage cells (OLCs) to proliferate, differentiate, and myelinate. We hypothesize that aberrant neuronal activity associated with epilepsy may affect the OLC response. For our experiments we have used a mouse model of FCD created by intrauterine electroporation of a plasmid carrying a mutated mTOR gene into neuronal progenitors, leading to hyperactivity of the mTOR signaling cascade in cortical layer 2/3 excitatory neurons. The occurrence of epileptic seizures was assessed by continuous video-EEG monitoring. We quantified the number of OLCs in grey matter (L2-L3) and white matter (corpus callosum) in dysplastic and contralateral cortical hemispheres in FCD mice. Mice electroporated with GFP plasmid were used as controls. We have found that FCD is accompanied by a loss of OLC numbers within the cortical lesion. This phenomenon might be potentially attributed to non cell-autonomous signaling by neurons with increased mTOR activity rather than to the seizures themselves. Furthermore, our findings support the concept of activity-dependent myelination in the corpus callosum but not in the cortex. Supported by: PRIMUS/21/MED/005; LX22NPO5107; AZV (NU21-08-00533, NU21-04-00601); Czech Science Foundation 21-17564S; ERDF-Project Brain Dynamics CZ.02.01.01/00/22_008/0004643.