Reduction of Hippocampal High-Frequency Activity in Wag/Rij Rats with a Genetic Predisposition to Absence Epilepsy

Abstract

In temporal lobe epilepsy, high frequency oscillations serve as electroencephalographic (EEG) markers of epileptic hippocampal tissue. In contrast, absence epilepsy and other idiopathic epilepsies are known to result from thalamo-cortical abnormalities, with the hippocampus involvement considered to be only indirect. We aimed to uncover the role of the hippocampus in absence epilepsy using a genetic rat model of absence epilepsy (WAG/Rij rats), in which spike-wave discharges (SWDs) appear spontaneously in cortical EEG. We performed simultaneous recordings of local field potential from the hippocampal dentate gyrus using pairs of depth electrodes and epidural cortical EEG in freely moving rats. Hippocampal ripples (100–200 Hz) and high frequency oscillations (HFO, 50–70 Hz) were detected using GUI RIPPLELAB in MatLab (Navarrete et al., 2016). Based on the dynamics of hippocampal ripples, SWDs were divided into three clusters, which might represent different seizure types in reference to the involvement of hippocampal processes. This might underlie impairment of hippocampus-related cognitive processes in some patients with absence epilepsy. A significant reduction to nearly zero-ripple-density was found 4–8 s prior to SWD onset and during 4 s immediately after SWD onset. It follows that hippocampal ripples were not just passively blocked by the onset of SWDs, but they were affected by spike-wave seizure initiation mechanisms. Hippocampal HFO were reduced during the preictal, ictal and postictal periods in comparison to the baseline. Therefore, hippocampal HFO seemed to be blocked with spike-wave seizures. All together, this might underlie impairment of hippocampus-related cognitive processes in some patients with absence epilepsy. Further investigation of processes underlying SWD-related reduction of hippocampal ripples and HFO oscillations may help to predict epileptic attacks and explain cognitive comorbidities in patients with absence epilepsy.