Neuronal synchrony and the transition to spontaneous seizures

Grasse, Dane W.; Karunakaran, Suganya; Moxon, Karen A.

doi:10.1016/j.expneurol.2013.05.004

Cited by 105 publications

(91 citation statements)

References 71 publications

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“…A decrease in neuronal activity of principal cells at seizure onset was recently confirmed during partial seizures recorded in the hippocampus of epileptic rats after pilocarpine-induced "status epilepticus" (Grasse et al 2013). In this study of unit activity performed with tetrode electrodes, the decrease in firing gener- ated by principal neurons was preceded by an increase in the activity of units identified as inhibitory interneurons.…”

Section: Seizure Onsetmentioning

confidence: 76%

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

Curtis

Avoli

2015

Cold Spring Harb Perspect Med

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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.

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Section: Seizure Onsetmentioning

confidence: 76%

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

Curtis

Avoli

2015

Cold Spring Harb Perspect Med

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“…Previous work demonstrated that inhibitory hippocampal neurons display progressive synchrony and increased firing rates minutes before the onset of pyramidal neuron hyperexcitability and sustained ictal spiking (29,30). Thus, increased I Na,P in CA3 Scn8a N1768D/+ inhibitory neurons may be critical in the preictal transition to spontaneous seizures in mutant hippocampus.…”

Section: Discussionmentioning

confidence: 99%

Neuronal hyperexcitability in a mouse model of SCN8A epileptic encephalopathy

Lopez-Santiago

Yuan

Wagnon

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Patients with early infantile epileptic encephalopathy (EIEE) experience severe seizures and cognitive impairment and are at increased risk for sudden unexpected death in epilepsy (SUDEP). EIEE13 [Online Mendelian Inheritance in Man (OMIM) # 614558] is caused by de novo missense mutations in the voltage-gated sodium channel gene SCN8A. Here, we investigated the neuronal phenotype of a mouse model expressing the gain-of-function SCN8A patient mutation, p.Asn1768Asp (Na v 1.6-N1768D). Our results revealed regional and neuronal subtype specificity in the effects of the N1768D mutation. Acutely dissociated hippocampal neurons from Scn8a N1768D/+ mice showed increases in persistent sodium current (I Na ) density in CA1 pyramidal but not bipolar neurons. In CA3, I Na,P was increased in both bipolar and pyramidal neurons. Measurement of action potential (AP) firing in Scn8a N1768D/+ pyramidal neurons in brain slices revealed early afterdepolarization (EAD)-like AP waveforms in CA1 but not in CA3 hippocampal or layer II/III neocortical neurons. The maximum spike frequency evoked by depolarizing current injections in Scn8a N1768D/+ CA1, but not CA3 or neocortical, pyramidal cells was significantly reduced compared with WT. Spontaneous firing was observed in subsets of neurons in CA1 and CA3, but not in the neocortex. The EAD-like waveforms of Scn8a N1768D/+ CA1 hippocampal neurons were blocked by tetrodotoxin, riluzole, and SN-6, implicating elevated persistent I Na and reverse mode Na/Ca exchange in the mechanism of hyperexcitability. Our results demonstrate that Scn8a plays a vital role in neuronal excitability and provide insight into the mechanism and future treatment of epileptogenesis in EIEE13.sodium channel | epilepsy | mouse model | action potential | Na/Ca exchange

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“…Epilepsia ILAE enhancement (Fig. 2Ba); such a pattern could be identified in >150 principal cells and about 50 interneurons recorded during several focal seizures 18 ( Fig. 2Bb).…”

Section: Initiation Of Focal Seizuresmentioning

confidence: 99%

“…[18][19][20] These studies have shown that the initial 5-10 s of a seizure correlate with a virtual cease of principal neuron activity along with interneuron firing Intracerebral signals recorded with multichannel stereo-EEG recording electrodes in a patient with a right frontal cortical dysplasia during presurgical monitoring. The onset of the seizure (arrows) correlates with low-voltage fast activity in the epileptogenic zone (contacts A3, B3, B4, C4, C5, C6, and D3 recorded with multichannel depth electrodes).…”

Section: Initiation Of Focal Seizuresmentioning

confidence: 99%

GABAergic networks jump‐start focal seizures

2016

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SUMMARYAbnormally enhanced glutamatergic excitation is commonly believed to mark the onset of a focal seizure. This notion, however, is not supported by firm evidence, and it will be challenged here. A general reduction of unit firing has been indeed observed in association with low-voltage fast activity at the onset of seizures recorded during presurgical intracranial monitoring in patients with focal, drug-resistant epilepsies. Moreover, focal seizures in animal models start with increased c-aminobutyric acid (GABA)ergic interneuronal activity that silences principal cells. In vitro studies have shown that synchronous activation of GABA A receptors occurs at seizure onset and causes sizeable elevations in extracellular potassium, thus facilitating neuronal recruitment and seizure progression. A paradoxical involvement of GABAergic networks is required for the initiation of focal seizures characterized by low-voltage fast activity, which represents the most common seizure-onset pattern in focal epilepsies.

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Neuronal synchrony and the transition to spontaneous seizures

Cited by 105 publications

References 71 publications

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

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

Neuronal hyperexcitability in a mouse model of SCN8A epileptic encephalopathy

GABAergic networks jump‐start focal seizures

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