Hypoactivity of CA3 pyramidal neurons in the pilocarpine model of mesial temporal lobe epilepsy

Reduced CA3-driven interictal activity in hippocampal-entorhinal cortex (EC) slices obtained from pilocarpine-treated rodents is accompanied by the persistence of ictal discharges originating from EC. Therefore, loss of CA3 pyramidal cells could be critical for unveiling limbic seizures in mesial temporal lobe epilepsy (MTLE). We analyzed here this issue by means of in vitro and ex vivo imaging along with histopathology in pilocarpine-treated and age-matched, non-epileptic control (NEC) rats. By visualizing immunopositivity for FosB/ΔFosB-related proteins - which accumulate in the nuclei of seizing neurons - we found that activated neurons can be found in many hippocampal and parahippocampal regions but not in CA3. Intrinsic optical signal (IOS) analysis of the stimulus-induced responses in slices obtained 3 weeks after SE revealed that IOSs in CA3 were lower (p < 0.05) than in NEC slices following dentate gyrus stimulation, while comparable responses were elicited by stimuli delivered in the CA3 pyramidal layer. We conclude that in epileptic rats, and perhaps in MTLE patients, mechanisms other than neuronal loss hamper CA3 network synchronization and thus the ability of hippocampal outputs to control EC ictogenesis