Two different interictal spike patterns anticipate ictal activity in vitro

Abstract

4-Aminopyridine (4AP, 50 μM) induces interictal- and ictal-like discharges in brain slices including parahippocampal areas such as the entorhinal cortex (EC) but the relation between these two types of epileptiform activity remains undifined. Here, by employing field potential recordings in rat EC slices during 4AP application, we found that: (i) interictal events have a wide range of duration (0.4–3.3 s) and interval of occurrence (1.4–84 s); (ii) ictal discharges are either preceded by an isolated “slow” interictal discharge (ISID; duration=1.5±0.1 s, interval of occurrence=33.8±1.8 s) or suddenly initiate from a pattern of frequent polispike interictal discharge (FPID; duration=0.8±0.1 s; interval of occurrence=2.7±0.2 s); and (iii) ISID-triggered ictal events have longer duration (116±7.3 s) and interval of occurrence (425.8±42.3 s) than those initiating suddenly during FPID (58.3±7.8 s and 202.1±21.8 s, respectively). Glutamatergic receptor antagonists abolished ictal discharges in all experiments, markedly reduced FPIDs but did not influence ISIDs. We also discovered that high-frequency oscillations (HFOs, 80–500 Hz) occur more frequently during ISIDs as compared to FPIDs, and mainly coincide with the onset of ISID-triggered ictal discharges. These findings indicate that interictal events may define ictal onset features resembling those seen in vivo in low-voltage fast activity onset seizures. We propose a similar condition to occur in vivo in temporal lobe epileptic patients and animal models.

Keywords

• 4-Aminopyridine
• CA3 subfield
• Entorhinal cortex
• High frequency oscillations
• Ictogenesis