Operative GABAergic inhibition in hippocampal CA1 pyramidal neurons in experimental epilepsy

Esclapez, Monique; Hirsch, J F; Khazipov, Roustem; Ben‐Ari, Y.; Bernard, Christophe

doi:10.1073/pnas.94.22.12151

Cited by 125 publications

(85 citation statements)

References 30 publications

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“…For instance, robust periods of firing depression (presumably corresponding to IPSPs) have been recorded in electrophysiological studies performed presurgically with intracranial electrodes or extracellular unit recordings in TLE patients (Wilson and Engel, 1993;Isokawa-Akesson et al, 1989). Moreover, histochemical studies have demonstrated that some interneuron subtypes are preserved in both human and experimental animal epileptic tissue Davenport et al, 1990;Esclapez et al, 1997) even though some other subtypes are clearly decreased in number in specific limbic structures (de Guzman et al, 2006(de Guzman et al, , 2008.…”

Section: Gaba a Receptor-mediated Inhibition In Temporal Lobe Epilepsymentioning

confidence: 99%

“…Later studies, however, have challenged this assumption, by showing that inhibition per se or some types of inhibitory mechanisms are preserved in animal models of epilepsy (Davenport et al, 1990;Esclapez et al, 1997;Prince & Jacobs, 1998;Cossart et al, 2001Cossart et al, , 2005 and in post-surgical human temporal lobe tissue (Isokawa-Akesson et al, 1989;Babb et al, 1989;Avoli and Olivier, 1989;Avoli et al, 1995;Cohen et al, 2002). Moreover, more complex, at times ambiguous, roles for GABAergic signaling in epilepsy were identified.…”

Section: Introductionmentioning

confidence: 99%

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

Avoli¹,

Curtis²

2011

Progress in Neurobiology

227

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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Section: Gaba a Receptor-mediated Inhibition In Temporal Lobe Epilepsymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Avoli¹,

Curtis²

2011

Progress in Neurobiology

227

253

View full text Add to dashboard Cite

show abstract

“…In recent studies, inhibitory processes have been observed during different types of seizure activity (Esclapez et al 1997;Prince and Jacobs 1998;Prince et al 1997;Timofeev et al 2002b;Traub et al 1996). Recordings from human and rat slices (Cohen et al 2002;FujiwaraTsukamoto et al 2003) as well in vivo experiments in cats (Timofeev et al 2002b) have demonstrated that PDSs contain an important inhibitory component.…”

Section: Cellular Mechanisms Mediating Spike and Wave Dischargesmentioning

confidence: 99%

“…Accordingly, the traditional point of view is that the key intracellular correlate of epileptiform activity, the paroxysmal depolarizing shift (PDS), consists of a giant EPSP (Johnston and Brown 1981) enhanced by activation of voltageregulated intrinsic currents (de Curtis et al 1999;Dichter and Ayala 1987;Prince and Connors 1984;Westbrook and Lothman 1983;Wong and Prince 1978). It was therefore a surprise when more recent evidence showed that synaptic inhibition remains functional in many forms of paroxysmal activities (Cohen et al 2002;Davenport et al 1990;Engel et al 2003;Esclapez et al 1997;Higashima 1988;Prince and Jacobs 1998;Timofeev et al 2002b;Topolnik et al 2003;Traub et al 1996). Also, disruption of inhibitory function does not affect neocortical kindling (Denslow et al 2001), which is associated with an increases in synaptic strength that mediates recruitment of larger cortical areas (Teskey et al 2002).…”

Section: Introductionmentioning

confidence: 99%

Cellular and network mechanisms of electrographic seizures

Bazhenov

Timofeev

Fröhlich

et al. 2008

Drug Discovery Today: Disease Models

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Epileptic seizures constitute a complex multiscale phenomenon that is characterized by synchronized hyperexcitation of neurons in neuronal networks. Recent progress in understanding pathological seizure dynamics provides crucial insights into underlying mechanisms and possible new avenues for the development of novel treatment modalities. Here we review some recent work that combines in vivo experiments and computational modeling to unravel the pathophysiology of seizures of cortical origin. We particularly focus on how activity-dependent changes in extracellular potassium concentration affects the intrinsic dynamics of neurons involved in cortical seizures characterized by spike/wave complexes and fast runs.

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“…Clearly, in vitro analyses of hippocampi removed from post-SE epileptic animals, which exhibit widespread brain damage and seizures of undetermined origin (Bertram, 1997;Bertram et al, 2001;Harvey and Sloviter, 2005), may tend to underemphasize the epileptogenic contribution of the unexamined extrahippocampal structures, and to overemphasize the importance of the hippocampus by assuming, but not demonstrating, that the hippocampi of epileptic animals are "epileptic" (Tauck and Nadler, 1985;Wuarin and Dudek, 1996;Esclapez et al, 1997;Cossart et al, 2001;Bernard et al, 2004).…”

Section: Possible Functional Implicationsmentioning

confidence: 99%

Kainic acid‐induced recurrent mossy fiber innervation of dentate gyrus inhibitory interneurons: Possible anatomical substrate of granule cell hyperinhibition in chronically epileptic rats

Sloviter

Zappone

Harvey

et al. 2005

J of Comparative Neurology

145

110

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Kainic acid-induced neuron loss in the hippocampal dentate gyrus may cause epileptogenic hyperexcitability by triggering the formation of recurrent excitatory connections among normally unconnected granule cells. We tested this hypothesis by assessing granule cell excitability repeatedly within the same awake rats at different stages of the synaptic reorganization process initiated by kainate-induced status epilepticus (SE). Granule cells were maximally hyperexcitable to afferent stimulation immediately after SE, and became gradually less excitable during the first month post-SE. The chronic epileptic state was characterized by granule cell hyperinhibition, i.e. abnormally increased paired-pulse suppression and an abnormally high resistance to generating epileptiform discharges in response to afferent stimulation. Focal application of the GABA A receptor antagonist bicuculline methiodide within the dentate gyrus abolished the abnormally increased paired-pulse suppression recorded in chronically hyperinhibited rats. Combined Timm staining and parvalbumin immunocytochemistry revealed dense innervation of dentate inhibitory interneurons by newly-formed, Timm-positive, mossy fiber terminals. Ultrastructural analysis by conventional-and post-embedding GABA immunocytochemical electron microscopy confirmed that abnormal mossy fiber terminals of the dentate inner molecular layer formed frequent asymmetrical synapses with inhibitory interneurons and with GABA-immunopositive dendrites, as well as with GABA-immunonegative dendrites of presumed granule cells. These results in chronically epileptic rats demonstrate that dentate granule cells are maximally hyperexcitable immediately after SE, prior to mossy fiber sprouting, and that synaptic reorganization following kainate-induced injury is temporally associated with GABA A receptor-dependent granule cell hyperinhibition, rather than an hypothesized progressive hyperexcitability. The anatomical data provide evidence of a possible anatomical substrate for the chronically hyperinhibited state.

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Operative GABAergic inhibition in hippocampal CA1 pyramidal neurons in experimental epilepsy

Cited by 125 publications

References 30 publications

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

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

Cellular and network mechanisms of electrographic seizures

Kainic acid‐induced recurrent mossy fiber innervation of dentate gyrus inhibitory interneurons: Possible anatomical substrate of granule cell hyperinhibition in chronically epileptic rats

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