Impaired activation of CA3 pyramidal neurons in the epileptic hippocampus |
| |
Authors: | Giuseppe Biagini Giovanna D’Arcangelo Enrica Baldelli Margherita D’Antuono Virginia Tancredi Massimo Avoli |
| |
Institution: | (1) Dipartimento di Scienze Biomediche, Università di Modena e Reggio Emilia, 41100 Modena, Italy;(2) Dipartimento di Neuroscienze, Università di Roma ‘Tor Vergata,’, 00173 Roma, Italy;(3) Montreal Neurological Institute and Department of Neurology and Neurosurgery, McGill University, H3A 2B4 Montreal, QC, Canada;(4) Dipartimento di Fisiologia Umana e Farmacologia ‘V. Erspamer,’, Università di Roma ‘La Sapienza,’, 00185 Roma, Italy |
| |
Abstract: | 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. Pilocarpinetreated 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/ΔFosBrelated proteins—which accumulate in the nuclei of neurons activated by seizures—we found that: (1) 24 h after
SE, FosB/ΔFosB immunoreactivity was absent in medial EC layer III, but abundant in dentate gyrus, hippocampus proper (including
CA3) and subiculum; (2) FosB/ΔFosB levels progressively diminished 3 and 7 d after SE, whereas remaining elevated (p<0.01) in subiculum; (3) FosB/ΔFosB 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 comparision with other epileptic limbic areas. We propose that this feature may
affect the ability of hippocampal outputs to control epileptiform synchronization in EC. |
| |
Keywords: | Entorhinal cortex hippocampus immediate early genes intrinsic optical signals pilocarpine temporal lobe epilepsy |
本文献已被 PubMed SpringerLink 等数据库收录! |
|