Evolution of interictal activity in models of mesial temporal lobe epilepsy.

Interictal activity and seizures are the hallmarks of focal epileptic disorders (which include mesial temporal lobe epilepsy, MTLE) in humans and in animal models. Interictal activity, which is recorded with cortical and intracerebral EEG recordings, comprises spikes, sharp waves and high-frequency oscillations, and has been used in clinical practice to identify the epileptic zone. However, its relation with seizures remains debated. Moreover, it is unclear whether specific EEG changes in interictal activity occur during the time preceding the appearance of spontaneous seizures. This period, which is termed "latent", has been studied in rodent models of MTLE in which spontaneous seizures start to occur following an initial insult (most often a status epilepticus induced by convulsive drugs such as kainic acid or pilocarpine) and may mirror epileptogenesis, i.e., the process leading the brain to develop an enduring predisposition to seizure generation. Here, we will address this topic by reviewing experimental studies performed in MTLE models. Specifically, we will review data highlighting the dynamic changes in interictal spiking activity and high-frequency oscillations occurring during the latent period, and how optogenetic stimulation of specific cell populations can modulate them in the pilocarpine model. These findings indicate that interictal activity: (i) is heterogeneous in its EEG patterns and thus, presumably, in its underlying neuronal mechanisms; and (ii) can pinpoint to the epileptogenic processes occurring in focal epileptic disorders in animal models and, perhaps, in epileptic patients.

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

Interictal spikes and high-frequency oscillations (HFOs, ripples: 80-200 â€‹Hz, fast ripples: 250-500 â€‹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 â€‹= â€‹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 â€‹= â€‹1 655) and type 2 (n â€‹= â€‹2 309) interictal spikes were significantly lower during the late phase of the latent period compared to its early and mid phase (p â€‹< â€‹0.001). However, rates of type 1 spikes associated with ripples (n â€‹= â€‹266) or fast ripples (n â€‹= â€‹106), as well as rates of type 2 interictal spikes associated with ripples (n â€‹= â€‹233), were significantly higher during the late phase compared to the early and mid phases (p â€‹< â€‹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.