Spontaneous and evoked high-frequency oscillations in the tetanus toxin model of epilepsy

Abstract

High-frequency oscillations (HFOs) are an emerging biomarker for epileptic tissue. Yet the mechanism by which HFOs are produced is unknown, and their rarity makes them difficult to study. Our objective was to examine the occurrence of HFOs in relation to action potentials (APs) and the effect of microstimulation in the tetanus toxin (TT) model of epilepsy, a nonlesional model with a short latency to spontaneous seizures. Rats were injected with TT into dorsal hippocampus and implanted with a 16-channel (8 × 2) multielectrode array, one row each in CA3 and CA1. After onset of spontaneous seizures (3-9 days), recordings were begun of APs and local field potentials, analyzed for the occurrence of interictal spikes and HFOs. Recordings were made during microstimulation of each electrode using customized, open-source software. Population bursts of APs during interictal spikes were phase-locked with HFOs, which were observable almost exclusively with high-amplitude interictal spikes. Furthermore, HFOs could reliably be produced by microstimulation of the hippocampus, providing evidence that these oscillations can be controlled temporally by external means. We show for the first time the occurrence of HFOs in the TT epilepsy model, an attractive preparation for their experimental investigation and, importantly, one with a different etiology than that of status models, providing further evidence of the generality of HFOs. The ability to provoke HFOs with microstimulation may prove useful for better understanding of HFOs by directly evoking them in the lab, and designing high-throughput techniques for presurgical localization of the epileptic focus.