Unit firing and oscillations at seizure onset in epileptic rodents

Abstract

Epileptic seizures result from a variety of pathophysiological processes, evidenced by different electrographic ictal onset patterns, as seen on direct brain recordings. The two most common electrographic patterns of focal ictal onset in patients are hypersynchronous (HYP) and lowvoltage fast (LVF). Whereas LVF ictal onsets were believed to result from disinhibition; based on similarities with absence seizures, focal HYP ictal onsets were believed to result from increased synchronizing inhibition. Recent findings, however, suggest the differences between these seizure onset types are more complicated and, in some cases, the opposite of these concepts are true. The following review presents evidence that a reduction of tonic inhibition on small pathologically interconnected neuron (PIN) clusters generating pathological high-frequency oscillations (pHFOs), which reflect abnormal synchronously bursting neurons may be the cause of HYP ictal onsets. Increased inhibition preceding LVF ictal onsets are discussed in other reviews in this issue. We postulate that neuronal cell loss following epileptogenic insults can result in structural reorganization, giving rise to small PIN clusters, which generate pHFOs. These clusters have a heterogeneous distribution and are spatially stable over time. Studies have demonstrated that a transient reduction in tonic inhibition causes these clusters to increase in size. This could result in consolidation and synchronization of pHFOs until a critical mass leads to propagation of HYP ictal discharges. Viewed within a network neuroscience framework, local disturbances such as PIN clusters are likely to contribute to large-scale brain network alterations: a better understanding of these epileptogenic networks promises to elucidate mechanisms of ictogenesis, epileptogenesis, and certain comorbidities of epilepsy.

Drug‐resistant epilepsy and the hypothesis of intrinsic severity: What about the high‐frequency oscillations?

“…Results from the intrahippocampal kainic acid and fluid percussion injury models suggest pathological HFOs could be an electrophysiological biomarker of epileptogenesis. The neuronal mechanisms of epileptogenesis could be due to the formation of PIN clusters 69 . After an episode of status epilepticus or a traumatic brain injury, PIN clusters could form and, through a kindling‐like process, lead to the formation of widespread PIN clusters (Figure 1).…”

CB1-Antibody Modified Liposomes for Targeted Modulation of Epileptiform Activities Synchronously Detected by Microelectrode Arrays

“…Investigations have revealed that changes in activities of inhibitory interneurons and excitatory pyramidal neurons contributed to onset and maintenance of TLE seizures. These types of neurons performed different discharge activities and developed distinct oscillatory phases , resulting in distinct seizure patterns . In this study, neural discharges of interneurons and pyramidal neurons were extracted from recorded signals.…”

Translational perspectives: Interneurones start seizures

“…), fast rhythmic neocortical busting has been attributed to start spike‐and‐wave discharges in cats (Timofeev & Steriade ), pathologically interconnected bursting neurones were speculated to start hypersynchronous ictal‐onset seizure activity in rodents (Li et al . ) and an increase in bursting propensity has been linked to peritumoural epileptogenic human tissue (Köhling et al . ).…”

“…From the 1970s onward, textbook knowledge holds that seizures are initiated by overexcitation; indeed, in many textbooks, the classic figure of Ayala et al (1973) is featured, showing a bursting neurone starting interictal spikes and seizure activity in the penicillin-focus model. Subsequently, an increase in intrinsic hippocampal neuronal bursting has been correlated with post-status epilepticus models in rodents (Chen et al 2011), fast rhythmic neocortical busting has been attributed to start spike-and-wave discharges in cats (Timofeev & Steriade 2004), pathologically interconnected bursting neurones were speculated to start hypersynchronous ictal-onset seizure activity in rodents (Li et al 2019) and an increase in bursting propensity has been linked to peritumoural epileptogenic human tissue (Köhling et al 2006). On the other hand, low-voltage fast Translational Perspectives J Physiol 597.23 ictal onset activity in patients was shown to coincide with a reduction in the firing of large numbers of neurones recorded intracranially (Truccolo et al 2011), along with preserved excitatory-inhibitory connections and sparse firing.…”