Two different interictal spike patterns anticipate ictal activity in vitro

Neurobiology of Disease

2015

Self Cite

GABA A receptor-mediated inhibition is active and may contribute to epileptiform synchronization. The efficacy of inhibition relies on low levels of intracellular Cl − , which are controlled by KCC2 activity. This evidence has led us to analyze with field potential recordings the effects induced by the KCC2 blockers VU0240551 (10 μM) or bumetanide (50 μM) and by the KCC2 enhancer CLP257 (100 μM) on the epileptiform discharges generated by piriform and entorhinal cortices (PC and EC, respectively) in an in vitro brain slice preparation. Ictal-and interictal-like discharges along with high-frequency oscillations (HFOs, ripples: 80-200 Hz, fast ripples: 250-500 Hz) were recorded from these two regions during application of 4-aminopyridine (4AP, 50 μM). Blocking KCC2 activity with either VU024055 or high doses of bumetanide abolished ictal discharge in both PC and EC; in addition, these experimental procedures decreased the interval of occurrence and duration of interictal discharges. In contrast, enhancing KCC2 activity with CLP257 increased ictal discharge duration in both regions. Finally, blocking KCC2 activity decreased the duration and amplitude of pharmacologically isolated synchronous GABAergic events whereas enhancing KCC2 activity led to an increase in their duration. Our data demonstrate that in vitro ictogenesis is abolished or facilitated by inhibiting or enhancing KCC2 activity, respectively. We propose that these effects may result from the reduction of GABA A receptor-dependent increases in extracellular K + that are known to rest on KCC2 function.

Section: Modulation Of Isolated Gabaergic Events By Kcc2 Blockers Andsupporting

confidence: 91%

KCC2 function modulates in vitro ictogenesis

Hamidi

Neurobiology of Disease

2015

Self Cite

“…Low-voltage fast activity and hypersynchronous onset patterns can also be reproduced in a combined hippocampus-entorhinal cortex, or hippocampus amygdala slices perfused in vitro with either 4AP (Lopantsev and Avoli 1998;Avoli et al 2013b), low-magnesium and highpotassium solution (Derchansky et al 2006;Zhang et al 2012), as well as following highfrequency tetanic stimulation (Isomura et al 2008;Fujiwara-Tsukamoto et al 2010). In these in vitro models, low-voltage fast activity onset is characterized at the start by a prominent activation of inhibitory interneurons (Velazquez and Carlen 1999;Kohling et al 2000;Ziburkus et al 2006;Lasztoczi et al 2009;Fujiwara-Tsukamoto et al 2010), which transiently shut off principal cells ( Fig.…”

Section: Seizure Onsetmentioning

confidence: 88%

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

Curtis

Cold Spring Harb Perspect Med

2015

Self Cite

The neurophysiological patterns that correlate with partial (focal) seizures are well defined in humans by standard electroencephalogram (EEG) and presurgical depth electrode recordings. Seizure patterns with similar features are reproduced in animal models of partial seizures and epilepsy. However, the network determinants that support interictal spikes, as well as the initiation, progression, and termination of seizures, are still elusive. Recent findings show that inhibitory networks are prominently involved at the onset of these seizures, and that extracellular changes in potassium contribute to initiate and sustain seizure progression. The end of a partial seizure correlates with an increase in network synchronization, which possibly involves both excitatory and inhibitory mechanisms.

“…These two seizure onset types, which are also recorded in animal models both in vitro (Fig. 5C) [76][77][78] and in vivo (Fig. 5D) [42,45], suggest that the spiking dynamics occurring at the onset of a seizure may mirror different pathophysiological mechanisms.…”

Section: Interictal-ictal Interactionsmentioning

confidence: 70%

Mechanisms of Epileptiform Synchronization in Cortical Neuronal Networks

2014

CMC

Neuronal synchronization supports different physiological states such as cognitive functions and sleep, and it is mirrored by identifiable EEG patterns ranging from gamma to delta oscillations. However, excessive neuronal synchronization is often the hallmark of epileptic activity in both generalized and partial epileptic disorders. Here, I will review the synchronizing mechanisms involved in generating epileptiform activity in the limbic system, which is closely involved in the pathophysiogenesis of temporal lobe epilepsy (TLE). TLE is often associated to a typical pattern of brain damage known as mesial temporal sclerosis, and it is one of the most refractory adult form of partial epilepsy. This epileptic disorder can be reproduced in animals by topical or systemic injection of pilocarpine or kainic acid, or by repetitive electrical stimulation; these procedures induce an initial status epilepticus and cause 1-4 weeks later a chronic condition of recurrent limbic seizures. Remarkably, a similar, seizure-free, latent period can be identified in TLE patients who suffered an initial insult in childhood and develop partial seizures in adolescence or early adulthood. Specifically, I will focus here on the neuronal mechanisms underlying three abnormal types of neuronal synchronization seen in both TLE patients and animal models mimicking this disorder: (i) interictal spikes; (ii) high frequency oscillations (80-500 Hz); and (iii) ictal (i.e., seizure) discharges. In addition, I will discuss the relationship between interictal spikes and ictal activity as well as recent evidence suggesting that specific seizure onsets in the pilocarpine model of TLE are characterized by distinctive patterns of spiking (also termed preictal) and high frequency oscillations.