Impaired activation of CA3 pyramidal neurons in the epileptic hippocampus.
We employed in vitro and ex vivo imaging tools to characterize the function of limbic neuron networks in pilocarpine-treated and age-matched, nonepileptic control (NEC) rats. Pilocarpine-treated animals represent an established model of mesial temporal lobe epilepsy. Intrinsic optical signal (IOS) analysis of hippocampal-entorhinal cortex (EC) slices obtained from epileptic rats 3 wk after pilocarpine-induced status epilepticus (SE) revealed hyperexcitability in many limbic areas, but not in CA3 and medial EC layer III. By visualizing immunopositivity for FosB/DeltaFosB-related proteins which accumulate in the nuclei of neurons activated by seizures we found that: (1) 24 h after SE, FosB/DeltaFosB immunoreactivity was absent in medial EC layer III, but abundant in dentate gyrus, hippocampus proper (including CA3) and subiculum; (2) FosB/DeltaFosB levels progressively diminished 3 and 7 d after SE, whereas remaining elevated (p < 0.01) in subiculum; (3) FosB/DeltaFosB levels sharply increased 2 wk after SE (and remained elevated up to 3 wk) in dentate gyrus and in most of the other areas but not in CA3. A conspicuous neuronal damage was noticed in medial EC layer III, whereas hippocampus was more preserved. IOS analysis of the stimulus-induced responses in slices 3 wk after SE demonstrated that IOSs in CA3 were lower (p < 0.05) than in NEC slices following dentate gyrus stimulation, but not when stimuli were delivered in CA3. These findings indicate that CA3 networks are hypoactive in comparison with other epileptic limbic areas. We propose that this feature may affect the ability of hippocampal outputs to control epileptiform synchronization in EC.
Biagini
Giuseppe
G
Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia, 41100 Modena, Italy.
D'Arcangelo
Giovanna
G
Baldelli
Enrica
E
D'Antuono
Margherita
M
Tancredi
Virginia
V
Avoli
Massimo
M
D000818:Animals; D018891:Dentate Gyrus / Q000503:physiopathology; D004195:Disease Models, Animal; D004558:Electric Stimulation; D018728:Entorhinal Cortex / Q000503:physiopathology; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology*; D006624:Hippocampus / Q000503:physiopathology*; D009434:Neural Pathways / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D010862:Pilocarpine / Q000633:toxicity; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017966:Pyramidal Cells / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000139:chemically induced / Q000503:physiopathology*
C483820:Fosb protein, rat; D016760:Proto-Oncogene Proteins c-fos; D010862:Pilocarpine