Masking Synchronous GABA‐mediated Potentials Controls Limbic Seizures
2002; Wiley; Volume: 43; Issue: 12 Linguagem: Inglês
10.1046/j.1528-1157.2002.17402.x
ISSN1528-1167
AutoresMichaela Barbarosie, Jacques Louvel, Margherita D’Antuono, I. Kurcewicz, Massimo Avoli,
Tópico(s)Memory and Neural Mechanisms
ResumoSummary: Purpose: We determined how CA3‐driven interictal discharges block ictal activity generated in the entorhinal cortex during bath application of 4‐aminopyridine (4AP, 50 μ M ). Methods: Field potential and [K + ] o recordings were obtained from mouse combined hippocampus–entorhinal cortex slices maintained in vitro. Results: 4AP induced N ‐methyl‐ d ‐aspartate (NMDA) receptor–dependent ictal discharges that originated in the entorhinal cortex, disappeared over time, but were reestablished by cutting the Schaffer collateral (n = 20) or by depressing CA3 network excitability with local application of glutamatergic receptor antagonists (n = 5). In addition, two types of interictal activity occurred throughout the experiment. The first type was CA3 driven and was abolished by a non‐NMDA glutamatergic receptor antagonist. The second type was largely contributed by γ‐aminobutyric acid type A (GABA A ) receptor–mediated conductances and persisted during blockade of glutamatergic transmission. The absence of CA3‐driven interictal discharges in the entorhinal cortex after Schaffer collateral cut facilitated the GABA‐mediated interictal potentials that corresponded to large [K + ] o elevations and played a role in ictal discharge initiation. Accordingly, ictal discharges along with GABA‐mediated interictal potentials disappeared during GABA A ‐receptor blockade (n = 7) or activation of μ‐opioid receptors that inhibit GABA release (n = 4). Conclusions: Our findings suggest that CA3‐driven interictal events restrain ictal discharge generation in the entorhinal cortex by modulating the size of interictal GABA‐mediated potentials that lead to large [K + ] o elevations capable of initiating ictal discharges in this structure.
Referência(s)