Extrahippocampal high‐frequency oscillations during epileptogenesis

Abstract

The current study aimed to investigate the spatial and temporal patterns of high-frequency oscillations (HFOs) in the intra-/extrahippocampal areas during epileptogenesis. Local field potentials were bilaterally recorded from hippocampus (CA1), thalamus, motor cortex, and prefrontal cortex in 13 rats before and after intrahippocampal kainic acid (KA) lesions. HFOs in the ripple (100-200 Hz) and fast ripple (250-500 Hz) ranges were detected and their rates were computed during different time periods (1-5 weeks) after KA-induced status epilepticus (SE). Recurrent spontaneous seizures were observed in 7 rats after SE, and the other 6 rats did not develop epilepsy. During the latent period, the rate of hippocampal HFOs increased at the ipsilateral site of the KA lesion in both groups, and the HFO rate was significantly higher in the animals that later developed epilepsy. Animals that later developed epilepsy also demonstrated widespread appearance of HFOs, in both the ripple and the fast ripple range, whereas animals that did not develop epilepsy only exhibited changes in the ipsilateral intrahippocampal HFO rate. This study demonstrates an association between an increased rate of widespread HFOs and the later development of epilepsy, suggesting the formation of large-scale distributed pathological networks during epileptogenesis.

Ripple‐related firing of identified deep CA1 pyramidal cells in chronic temporal lobe epilepsy in mice

“…The latter experiments were performed during the latent period of epileptogenesis (1‐4 weeks after status). Of note, their results do show a slight down‐trend in the frequency of SWRs and FRs at the end of their recording period (week 5) . Given that we are looking at dramatically different time points, and that our area of interest is outside of the origin of status (ie, the primary focus), we do not consider our results contradictory.…”

“…Although we show an overall decrease in SWR frequency in epileptic mice, there are other studies that have shown the opposite. Notably, in the intrahippocampal kainate model of TLE, the rats that go on to develop epilepsy exhibit increased numbers of both ripples (similar to our SWRs) and FRs in the hippocampus . The latter experiments were performed during the latent period of epileptogenesis (1‐4 weeks after status).…”

“…Of note, their results do show a slight down-trend in the frequency of SWRs and FRs at the end of their recording period (week 5). 62 Given that we are looking at dramatically different time points, and that our area of interest is outside of the origin of status (ie, the primary focus), we do not consider our results contradictory. Instead, we emphasize that further studies should investigate the properties of all SFIs together during the initial epileptogenic insult, the latent period, and over time during the phase of chronic seizures, both close to the primary focus and within the secondary seizure spread zone.…”

“…Notably, in the intrahippocampal kainate model of TLE, the rats that go on to develop epilepsy exhibit increased numbers of both ripples (similar to our SWRs) and FRs in the hippocampus. 62 The latter experiments were performed during the latent period of epileptogenesis (1-4 weeks after status). Of note, their results do show a slight down-trend in the frequency of SWRs and FRs at the end of their recording period (week 5).…”

Changes in Physiological and Pathological Behaviours Produced by Deep Microelectrode Implantation Surgery in Rats: A Temporal Analysis

“…One example is research involving seizures and epilepsy models in which electrophysiological parameters, such as high-frequency oscillations, which are known to be associated with the disease are studied without regard to the possible effects of surgery. Moreover, these surgeries typically involve specific brain areas, such as the hippocampus and cortex; these areas contain circuits that are associated with the cognitive process through theta and gamma rhythms and ripple events and with specific physiological behaviours, such as the sleep-wake cycle [10][11][12]. Most of these surgeries involve the implantation of electrodes or microelectrodes into the brain for the purpose of recording electrical signals and/or the implantation of guide cannulas that are used to insert dialysis probes or fine needles for drug administration [10][11][12][13].…”