Two Seizure-Onset Types Reveal Specific Patterns of High-Frequency Oscillations in a Model of Temporal Lobe Epilepsy

Abstract

High-frequencyoscillations(HFOs;80 -500Hz)arethoughttomirrorthepathophysiologicalchangesoccurringinepilepticbrains.However,the distribution of HFOs during seizures remains undefined. Here, we recorded from the hippocampal CA3 subfield, subiculum, entorhinal cortex, and dentate gyrus to quantify the occurrence of ripples (80 -200 Hz) and fast ripples (250 -500 Hz) during low-voltage fast-onset (LVF) and hypersynchronous-onset (HYP) seizures in the rat pilocarpine model of temporal lobe epilepsy. We discovered in LVF seizures that (1) progressionfrompreictaltoictalactivitywascharacterizedinseizure-onsetzonesbyanincreaseofrippleratesthatwerehigherwhencomparedwithfast ripple rates and (2) ripple rates during the ictal period were higher compared with fast ripple rates in seizure-onset zones and later in regions of secondary spread. In contrast, we found in HYP seizures that (1) fast ripple rates increased during the preictal period and were higher compared with ripple rates in both seizure-onset zones and in regions of secondary spread and (2) they were still higher compared with ripple rates in both seizure-onset zones and regions of secondary spread during the ictal period. Our findings demonstrate that ripples and fast ripples show distinct time-and region-specific patterns during LVF and HYP seizures, thus suggesting that they play specific roles in ictogenesis.

Initiation, Propagation, and Termination of Partial (Focal) Seizures

“…These two patterns may be the expression of the activation of the same networks, because the large-amplitude spikes typically detected in the hypersynchronous pattern are often followed by short runs of low-voltage fast activity (Perucca et al 2014). In line with the concept of the epileptic network, experimental work has shown that both patterns are generated by the limbic system in vivo in the pilocarpine model of mesial TLE (Levesque et al 2012), and in the in vitro whole guinea pig brain treated with different proconvulsive drugs, such as bicuculline or 4-aminopyridine (4AP) (Uva et al 2005;Carriero et al 2010;Boido et al 2014a).…”

“…Evolving patterns are commonly observed in posttraumatic and poststroke epilepsy models (Pitkänen et al 2006;Kadam et al 2010), in models of mesial TLE either secondary to pharmacologically induced status epilepticus (Williams et al 2009;Bortel et al 2010;Levesque et al 2012), or induced by kindling (Michalakis et al 1998). As in humans, seizures in experimental animals with partial epilepsy occur randomly, often in clusters (Grabenstatter et al 2005;Goffin et al 2007;Williams et al 2009).…”

“…Both low-voltage fast activity and hypersynchronous seizure-onset patterns are typically observed in animal models of mesial TLE (Engel et al 1990;Bragin et al 1999;Levesque et al 2012) and in models of acute temporal seizures (Bragin et al 1999;Zhang et al 2012;Levesque et al 2013;Boido et al 2014a). These two patterns may be the expression of the activation of the same networks, because the large-amplitude spikes typically detected in the hypersynchronous pattern are often followed by short runs of low-voltage fast activity (Perucca et al 2014).…”

Linking kindling to increased glutamate release in the dentate gyrus of the hippocampus through the STXBP5/tomosyn‐1 gene

“…Bragin, Azizyan, Almajano, Wilson, and Engel (2005) have shown low‐voltage fast‐onset (LVF) and hypersynchronous‐onset (HYP) spikes preceding spontaneous seizures in freely moving rats that had SE‐induced kainic acid hippocampal injections. Levesque, Salami, Gotman, and Avoli (2012) demonstrated LVF and HYP in the rat pilocarpine model of TLE. Avoli and colleagues have recently studied the equivalent of LVF and HYP seizures in an in vitro slice preparation of rat perirhinal cortex (Köhling et al., 2016).…”

Silencing Hyper-Excitable Neurons as a Treatment for Status Epilepticus and Temporal Lobe Epilepsy.

“…Studies from animal models of epilepsy have revealed multiple sites where seizures begin such as amygdala (Bertram 1997), midline dorsal thalamus (Bertram, Mangan et al 2001), and parts of hippocampal formation (Lévesque, Salami et al 2012). …”