20220076 |
Carriero G, Uva L, Gnatkovsky V, Avoli M, de Curtis M: Independent epileptiform discharge patterns in the olfactory and limbic areas of the in vitro isolated guinea pig brain during 4-aminopyridine treatment. J Neurophysiol. 2010 Mar 10. In vitro studies performed on brain slices have demonstrated that the K+-channel blocker 4-aminopyridine (4AP, 50muM) discloses electrographic seizure activity and interictal discharges with peculiar pharmacological profiles. These epileptiform patterns have been further analyzed here in a close-to-in-vivo guinea pig brain preparation by using field potential recordings in olfactory and limbic structures. We identified a reproducible sequence of epileptiform events. Runs of fast oscillatory activity (fast runs, FRs) in the piriform cortex (PC) propagated to the lateral entorhinal cortex (EC), hippocampus and occasionally to the medial EC. FRs features developed over time: early and late FRs were char-acterized by different duration (1.78+/-0.51 mean+/-SD and 27.95+/-4.55 sec, respectively), frequency of occurrence (every 1.82+/-0.49 sec and 34.16+/-6.03 sec, respectively) and frequency content (20-40 Hz vs. 40-60 Hz). FRs were asynchronously generated in the two hemispheres. Preictal spikes independent from the FRs appeared in the hippocampus/EC and developed into ictal-like discharges that did not propagate to the PC, where FRs continued to occur. Ictal-like activity in the limbic cortex consisted of (i) fast activity with onset either in the hippocampus (n=6) or in the mEC (n=2), followed by (ii) irregular spiking and (iii) sequences of diffusely synchronous bursts. Perfusion of the NMDA receptor antagonist AP5 (100microM) did not prevent FRs, increased the duration of limbic ictal-like discharges and favoured their propagation to olfactory structures. The AMPA receptor antagonist DNQX (50microM) blocked limbic ictal-like events and markedly reduced the amplitude of FRs, without affecting interictal events. In conclusion, 4AP induced epileptiform activities that are independent and asynchronous in the olfactory and in the hippocampal-entorhinal regions. Epileptiform discharges in limbic structures in the close-to-in-vivo guinea pig preparation show different pharmacological properties compared to in vitro slices obtained from rodents. |
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