Abstract <p>Febrile seizures (FS) in early childhood can lead to the developmentof epilepsy; however, in most cases, they resolve without consequences.The neurophysiological mechanisms that protect the brain from theeffects of FS remain poorly understood. It is also known that therisk of epilepsy significantly increases if a child has congenitalabnormalities in the structure of the cerebral cortex. In this study,we examined functional changes in the hippocampus of young ratssubjected to FS on the 10th postnatal day (P10) with freezing-inducedfocal cortical dysplasia (FCD) on P0. Experiments were conductedon three groups of animals: (1) control group (Ctrl)—rats withoutFS and FCD; (2) FS group—rats subjected to hyperthermia-inducedFS on P10; (3) FS+FCD group—rats with cortical freezing on P0 andFS on P10. Using recordings of local synaptic potentials in theCA1 region of the hippocampus, we found that FS led to significantchanges in synaptic transmission. In the FS group, there was anincrease in the threshold for population spike generation, a decreasein the synaptic transmission efficacy ratio, and an increase in thepaired-pulse ratio. These changes indicate reduced activity of CA3-CA1glutamatergic synapses, which may represent a compensatory responsepreventing epileptogenesis. However, in the FS+FCD group, such compensatorychanges were absent: synaptic transmission parameters did not differfrom those in the control group. This suggests that FCD impedesthe activation of protective mechanisms in the hippocampus in responseto FS. Thus, the presence of cortical dysplasia may increase therisk of epilepsy following FS by blocking natural compensatory processes.Our results highlight the importance of studying the interactionbetween congenital cortical developmental abnormalities and the consequencesof FS for understanding the mechanisms of epileptogenesis.</p>