Evolution of interictal spiking during the latent period in a mouse model of mesial temporal lobe epilepsy

Abstract

Interictal spikes and high-frequency oscillations (HFOs, ripples: 80–200 ​Hz, fast ripples: 250–500 ​Hz) occur in epileptic patients and in animal models of mesial temporal lobe epilepsy (MTLE). In this study, we explored how type 1 and type 2 interictal spikes as well as ripples and fast ripples evolve during the latent period in the hippocampus of pilocarpine-treated mice. Depth EEG recordings were obtained from the hippocampus CA3 subfield of adult male mice (n ​= ​5, P60–P100) starting one day before pilocarpine-induced status epilepticus up to the first spontaneous seizure, the so-called latent period. We found that rates of type 1 (n ​= ​1 655) and type 2 (n ​= ​2 309) interictal spikes were significantly lower during the late phase of the latent period compared to its early and mid phase (p ​< ​0.001). However, rates of type 1 spikes associated with ripples (n ​= ​266) or fast ripples (n ​= ​106), as well as rates of type 2 interictal spikes associated with ripples (n ​= ​233), were significantly higher during the late phase compared to the early and mid phases (p ​< ​0.05). Our findings reveal that an increase of type 1 interictal spikes co-occurring with ripples or fast ripples and an increase of type 2 interictal spikes co-occurring with ripples mark the end of the latent period. We propose that changes in the occurrence of interictal spike associated with HFOs represent a biomarker of epileptogenicity in this mouse model of MTLE.

Keywords

• Mesial temporal lobe epilepsy
• Epileptogenesis
• Interictal spikes
• High-frequency oscillations
• Latent period
• Pilocarpine