Cellular Mechanism of Neuronal Synchronization in Epilepsy

Traub, Roger D.; Wong, Robert K. S.

doi:10.1126/science.7079735

Cited by 581 publications

(330 citation statements)

References 25 publications

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“…Slc4a10 was strongly expressed in CA3 pyramidal neurons that are well known for their propensity to generate physiological sharp waves, as well as pathological interictal events (25)(26)(27)(28)(29). Propionate application caused a transient decrease in the pH i in the WT CA3 pyramidal neurons and, with a similar time course, a suppression of 4-AP-induced interictal-like activity.…”

Section: Discussionmentioning

confidence: 90%

Mice with targeted Slc4a10 gene disruption have small brain ventricles and show reduced neuronal excitability

Jacobs

Ruusuvuori

Sipilä³

et al. 2008

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

148

248

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Members of the SLC4 bicarbonate transporter family are involved in solute transport and pH homeostasis. Here we report that disrupting the Slc4a10 gene, which encodes the Na ؉ -coupled Cl ؊ -HCO3 ؊ exchanger Slc4a10 (NCBE), drastically reduces brain ventricle volume and protects against fatal epileptic seizures in mice. In choroid plexus epithelial cells, Slc4a10 localizes to the basolateral membrane. These cells displayed a diminished recovery from an acid load in KO mice. Slc4a10 also was expressed in neurons. Within the hippocampus, the Slc4a10 protein was abundant in CA3 pyramidal cells. In the CA3 area, propionate-induced intracellular acidification and attenuation of 4-aminopyridineinduced network activity were prolonged in KO mice. Our data indicate that Slc4a10 is involved in the control of neuronal pH and excitability and may contribute to the secretion of cerebrospinal fluid. Hence, Slc4a10 is a promising pharmacological target for the therapy of epilepsy or elevated intracranial pressure.cerebrospinal fluid ͉ epilepsy ͉ ion transport ͉ knockout mouse ͉ pH regulation

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Section: Discussionmentioning

confidence: 90%

Mice with targeted Slc4a10 gene disruption have small brain ventricles and show reduced neuronal excitability

Jacobs

Ruusuvuori

Sipilä³

et al. 2008

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

148

248

View full text Add to dashboard Cite

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“…The propensity of the CA3 area to generate such a stereotyped interictal behavior is presumably caused by the presence of recurrent excitatory connections among neighboring CA3 pyramidal cells, along with their ability to generate voltage-gated Ca 2+ bursting Wong, 1983, 1987;Traub and Wong, 1982;Traub and Jefferys, 1994). When recorded intracellularly from hippocampal pyramidal cells, these 4AP-induced, CA3-driven interictal discharges are associated with action potential bursts riding on a depolarization (Fig.…”

Section: Fast Ca3-driven Interictal Activitymentioning

confidence: 99%

GABAergic synchronization in the limbic system and its role in the generation of epileptiform activity

Avoli¹,

Curtis²

2011

Progress in Neurobiology

224

253

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GABA is the main inhibitory neurotransmitter in the adult forebrain, where it activates ionotropic type A and metabotropic type B receptors. Early studies have shown that GABA A receptormediated inhibition controls neuronal excitability and thus the occurrence of seizures. However, more complex, and at times unexpected, mechanisms of GABAergic signaling have been identified during epileptiform discharges over the last few years. Here, we will review experimental data that point at the paradoxical role played by GABA A receptor-mediated mechanisms in synchronizing neuronal networks, and in particular those of limbic structures such as the hippocampus, the entorhinal and perirhinal cortices, or the amygdala. After having summarized the fundamental characteristics of GABA A receptor-mediated mechanisms, we will analyze their role in the generation of network oscillations and their contribution to epileptiform synchronization. Whether and how GABA A receptors influence the interaction between limbic networks leading to ictogenesis will be also reviewed. Finally, we will consider the role of altered inhibition in the human epileptic brain along with the ability of GABA A receptor-mediated conductances to generate synchronous depolarizing events that may lead to ictogenesis in human epileptic disorders as well.

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“…In cats, even simple prolonged maintenance under ketamine-xylazine anaesthesia leads to seizure activity in 30% of animals (Boucetta et al, 2008). These models led to the recognition that both intrinsic properties such as voltage-gated Ca 2+ currents (Schwartzkroin and Slawsky, 1977), pathologically large EPSPs (Johnston and Brown, 1981), recurrent excitatory networks (Traub et al, 1993Traub and Wong, 1982), and depolarizing IPSPs and other currents (Timofeev, 2010) contribute to epileptic activity.…”

Section: Acute Models Of Epilepsy-convulsant Drugsand Changes In Extrmentioning

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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Cellular Mechanism of Neuronal Synchronization in Epilepsy

Cited by 581 publications

References 25 publications

Mice with targeted Slc4a10 gene disruption have small brain ventricles and show reduced neuronal excitability

Mice with targeted Slc4a10 gene disruption have small brain ventricles and show reduced neuronal excitability

GABAergic synchronization in the limbic system and its role in the generation of epileptiform activity

Mechanisms of physiological and epileptic HFO generation

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