High‐frequency synaptic input contributes to seizure initiation in the low‐[Mg<sup>2+</sup>] model of epilepsy

Lasztóczi, Bálint; Antal, Károly; Nyikos, Lajos; Emri, Zsuzsa; Kardos, Julianna

doi:10.1111/j.1460-9568.2004.03231.x

Cited by 39 publications

(53 citation statements)

References 49 publications

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“…A poor correlation between these intracellular signals and the local field potential further suggests that they reflect convergent synaptic barrage that is poorly synchronized between cells, especially for frequencies >60 Hz (Lasztoczi et al, 2004;Trevelyan, 2009). In regions with relatively intact inhibition, chloride currents flowing into the cells through GABA A receptors could even become synchronous in many neurons due to the high connectivity ratio of some interneurons that contribute to generate field events (Glickfeld et al, 2009;Lasztoczi et al, 2004;Oren et al, 2010).…”

Section: Single Cell Dynamics During a Wide Range Of Hfo In Epileptogmentioning

confidence: 99%

Mechanisms of physiological and epileptic HFO generation

Jefferys

Prida

Wendling

et al. 2012

Progress in Neurobiology

268

238

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High frequency oscillations (HFO) have a variety of characteristics: band-limited or broad-band, transient burst-like phenomenon or steady-state. HFOs may be encountered under physiological or under pathological conditions (pHFO). Here we review the underlying mechanisms of oscillations, at the level of cells and networks, investigated in a variety of experimental in vitro and in vivo models. Diverse mechanisms are described, from intrinsic membrane oscillations to network processes involving different types of synaptic interactions, gap junctions and ephaptic coupling. HFOs with similar frequency ranges can differ considerably in their physiological mechanisms. The fact that in most cases the combination of intrinsic neuronal membrane oscillations and synaptic circuits are necessary to sustain network oscillations is emphasized. Evidence for pathological HFOs, particularly fast ripples, in experimental models of epilepsy and in human epileptic patients is scrutinized. The underlying mechanisms of fast ripples are examined both in the light of animal observations, in vivo and in vitro, and in epileptic patients, with emphasis on single cell dynamics. Experimental observations and computational modeling have led to hypotheses for these mechanisms, several of which are considered here, namely the role of out-ofphase firing in neuronal clusters, the importance of strong excitatory AMPA-synaptic currents and recurrent inhibitory connectivity in combination with the fast time scales of IPSPs, ephaptic coupling and the contribution of interneuronal coupling through gap junctions. The statistical behaviour of fast ripple events can provide useful information on the underlying mechanism and can help to further improve classification of the diverse forms of HFOs.

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Section: Single Cell Dynamics During a Wide Range Of Hfo In Epileptogmentioning

confidence: 99%

Mechanisms of physiological and epileptic HFO generation

Jefferys

Prida

Wendling

et al. 2012

Progress in Neurobiology

268

238

View full text Add to dashboard Cite

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“…Although the direct excitatory action of GABA has been demonstrated in the neonatal brain (postnatal days Ͻ8) (Khazipov et al 2004;Rivera et al 1999;Tyzio et al 2007), other more complex ways of GABAergic excitation have been established in adult animals and in human epileptic brain (Cohen et al 2002;Epsztein et al 2006;Fujiwara-Tsukamoto et al 2003Kaila et al 1997;Lamsa and Kaila 1997;Marty and Llano 2005;Perez Velazquez 2003;Staley et al 1995). Transitory between neonatal and adult, slices from juvenile (P10-13) rat hippocampus are frequently used in experimental epilepsy research as they are more susceptible to develop seizures than slices from adults (Heinemann et al 1991;Köhling et al 2000;Lasztóczi et al 2004). Interestingly, experimental data supported either excitatory (Dhzala and Staley 2003b;Khazipov et al 2004) or inhibitory/shunting (Rivera et al 1999;Tyzio et al 2007) actions of GABAergic transmission at this age.…”

Section: Introductionmentioning

confidence: 99%

“…How synchronized activation of large neuronal populations-reflected by the large-amplitude EEG signal of seizures-is brought about is a question of high theoretical and clinical importance. In vivo high-frequency oscillations (HFOs) Ͼ200 Hz preferentially occur at the seizure onset (Bragin et al 2005;Jirsch et al 2006), a feature manifested in vitro (Dzhala and Staley 2003a;Khoshravani et al 2005;Lasztóczi et al 2004). This temporal alignment of HFOs and transition to seizures suggests a causal link between the two phenomena (Bragin et al 2000(Bragin et al , 2002Jirsch et al 2006;Lasztóczi et al 2004).…”

Section: Introductionmentioning

confidence: 99%

“…In vivo high-frequency oscillations (HFOs) Ͼ200 Hz preferentially occur at the seizure onset (Bragin et al 2005;Jirsch et al 2006), a feature manifested in vitro (Dzhala and Staley 2003a;Khoshravani et al 2005;Lasztóczi et al 2004). This temporal alignment of HFOs and transition to seizures suggests a causal link between the two phenomena (Bragin et al 2000(Bragin et al , 2002Jirsch et al 2006;Lasztóczi et al 2004). HFOs are linked to hyperexcitability and synchrony of neuronal networks, the two hallmarks of epileptiform activity (Le Van Quyen et al 2006;McCormick and Contreras 2001;Perez Velazquez and Carlen 2000;Traub et al 2001).…”

Section: Introductionmentioning

confidence: 99%

“…Juvenile rat hippocampal slices bathed in low- [Mg 2ϩ ] artificial cerebrospinal fluid (ACSF) express preictal discharge trains with increasing similarity to SLE onset, confinement of field potential (fp) HFOs (400 -800 Hz) to the start of discharges, and gradual emergence of synchronized synaptic currents onto CA3 pyramidal cells (Lasztóczi et al 2004). Although the contribution of these synchronized inputs to SLE initiation was documented (Lasztóczi et al 2004), the relative weight of GABAergic versus glutamatergic components has not been established.…”

Section: Introductionmentioning

confidence: 99%

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Synchronization of GABAergic Inputs to CA3 Pyramidal Cells Precedes Seizure-Like Event Onset in Juvenile Rat Hippocampal Slices

Lasztóczi

Nyitrai

Héja

et al. 2009

Journal of Neurophysiology

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Lasztóczi B, Nyitrai G, Héja L, Kardos J. Synchronization of GABAergic inputs to CA3 pyramidal cells precedes seizure-like event onset in juvenile rat hippocampal slices. J Neurophysiol 102: 2538 -2553, 2009. First published August 12, 2009 doi:10.1152/jn.91318.2008. Here we address how dynamics of glutamatergic and GABAergic synaptic input to CA3 pyramidal cells contribute to spontaneous emergence and evolution of recurrent seizure-like events (SLEs) in juvenile (P10-13) rat hippocampal slices bathed in low- [Mg 2ϩ ] artificial cerebrospinal fluid. In field potential recordings from the CA3 pyramidal layer, a short epoch of high-frequency oscillation (HFO; 400 -800 Hz) was observed during the first 10 ms of SLE onset. GABAergic synaptic input currents to CA3 pyramidal cells were synchronized and coincided with HFO, whereas the glutamatergic input lagged by ϳ10 ms. If the intracellular [Cl Ϫ ] remained unperturbed (cell-attached recordings) or was set high with whole cell electrode solution, CA3 pyramidal cell firing peaked with HFO and GABAergic input. By contrast, with low intracellular [Cl Ϫ ], spikes of CA3 pyramidal cells lagged behind HFO and GABAergic input. This temporal arrangement of HFO, synaptic input sequence, synchrony of GABAergic currents, and pyramidal cell firing emerged gradually with preictal discharges until the SLE onset. Blockade of GABA A receptormediated currents by picrotoxin reduced the inter-SLE interval and the number of preictal discharges and did not block recurrent SLEs. Our data suggest that dynamic changes of the functional properties of GABAergic input contribute to ictogenesis and GABAergic and glutamatergic inputs are both excitatory at the instant of SLE onset. At the SLE onset GABAergic input contributes to synchronization and recruitment of pyramidal cells. We conjecture that this network state is reached by an activity-dependent shift in GABA reversal potential during the preictal phase.

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Role of A‐type potassium currents in excitability, network synchronicity, and epilepsy

Fransén

Tigerholm

2010

Hippocampus

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A range of ionic currents have been suggested to be involved in distinct aspects of epileptogenesis. Based on pharmacological and genetic studies, potassium currents have been implicated, in particular the transient A-type potassium current (KA). Epileptogenic activity comprises a rich repertoire of characteristics, one of which is synchronized activity of principal cells as revealed by occurrences of for instance fast ripples. Synchronized activity of this kind is particularly efficient in driving target cells into spiking. In the recipient cell, this synchronized input generates large brief compound EPSPs. The fast activation and inactivation of KA lead us to hypothesize a potential role in suppression of such EPSPs. In this work, using computational modeling, we have studied the activation of KA by synaptic inputs of different levels of synchronicity. We find that KA participates particularly in suppressing inputs of high synchronicity. We also show that the selective suppression stems from the current's ability to become activated by potentials with high slopes. We further show that KA suppresses input mimicing the activity of a fast ripple. Finally, we show that the degree of selectivity of KA can be modified by changes to its kinetic parameters, changes of the type that are produced by the modulatory action of KChIPs and DPPs. We suggest that the wealth of modulators affecting KA might be explained by a need to control cellular excitability in general and suppression of responses to synchronicity in particular. We also suggest that compounds changing KA-kinetics may be used to pharmacologically improve epileptic status.

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High‐frequency synaptic input contributes to seizure initiation in the low‐[Mg²⁺] model of epilepsy

Cited by 39 publications

References 49 publications

Mechanisms of physiological and epileptic HFO generation

Mechanisms of physiological and epileptic HFO generation

Synchronization of GABAergic Inputs to CA3 Pyramidal Cells Precedes Seizure-Like Event Onset in Juvenile Rat Hippocampal Slices

Role of A‐type potassium currents in excitability, network synchronicity, and epilepsy

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High‐frequency synaptic input contributes to seizure initiation in the low‐[Mg2+] model of epilepsy

Cited by 39 publications

References 49 publications

Mechanisms of physiological and epileptic HFO generation

Mechanisms of physiological and epileptic HFO generation

Synchronization of GABAergic Inputs to CA3 Pyramidal Cells Precedes Seizure-Like Event Onset in Juvenile Rat Hippocampal Slices

Role of A‐type potassium currents in excitability, network synchronicity, and epilepsy

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High‐frequency synaptic input contributes to seizure initiation in the low‐[Mg²⁺] model of epilepsy