Network and pharmacological mechanisms leading to epileptiform synchronization in the limbic system in vitro

Avoli, Massimo; D’Antuono, Margherita; Louvel, J.; Köhling, Rüdiger; Biagini, Giuseppe; Pumain, R.; D’Arcangelo, Giovanna; Tancredi, Virginia

doi:10.1016/s0301-0082(02)00077-1

Cited by 410 publications

(398 citation statements)

References 226 publications

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“…Here we show they are restricted to electrodes sampling the seizure onset zone. Similar field potentials of larger amplitude precede ictal events in several in vitro models of epilepsy 6,14,[33][34][35] . Moreover, intracranial recordings show PID-like events preceding seizures in multiple focal human epilepsies originating in temporal 17 or extra temporal 36 ; hippocampal 17,18 or neocortical 37 regions, and associated with sclerosis 17,38 , malformation 39 , dysplasia or in macroscopically normal tissue 36 .…”

Section: Discussionmentioning

confidence: 89%

Glutamatergic pre-ictal discharges emerge at the transition to seizure in human epilepsy

et al. 2011

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Mechanisms involved in the transition to an epileptic seizure remain unclear. We studied this question in tissue slices from human subjects with mesial temporal lobe epilepsies. Ictal-like discharges were induced in the subiculum by increasing excitability together with an alkalinization or low Mg 2+ . During the transition, distinct pre-ictal discharges emerged concurrently with interictal events. Intracranial recordings from the mesial temporal cortex of epileptic subjects revealed similar discharges before seizures were restricted to seizure onset sites. In vitro, pre-ictal events spread faster, have a larger amplitude and a distinct initiation site than interictal discharges. They depend on glutamatergic mechanisms and are preceded by pyramidal cell firing, while interneuron firing precedes interictal events which depend on both glutamatergic and depolarizing GABAergic transmission. Once established, recurrence of these pre-ictal discharges triggers seizures. Thus the subiculum supports seizure generation and the transition to seizure involves a novel, emergent glutamatergic population activity.3

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Section: Discussionmentioning

confidence: 89%

Glutamatergic pre-ictal discharges emerge at the transition to seizure in human epilepsy

et al. 2011

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“…It has been demonstrated in these studies that ictal discharge generation in brain slices that have undergone a lesion of the Schaffer collateral is depressed throughout the period of stimulation. As discussed below (Section 8.2), this experimental evidence suggests that the functional integrity of hippocampal output neurons may represent a critical control point in TLE pathophysiogenesis and gives to GABAergic synchronization a role in epileptic disordes (see also Avoli et al, 2002).…”

Section: Ca3-driven Outputs Control the Expression Of Gabaergic Synchmentioning

confidence: 94%

“…5B). These long-lasting epileptiform events -which may represent the equivalent of ictal phenomena and/or of status epilepticus seen in patients and in animal models in vivo -are induced by experimental procedures that include the application of the K + channel blocker 4AP, the cholinergic agonist pilocarpine (Nagao et al, 1996), trains of high frequency electrical stimuli as well as increased [K + ] or removal of Mg 2+ in the bathing medium, or (Jefferys, 1990;Avoli, 1990Avoli, , 1996Avoli et al, 2002;Fujiwara-Tsukamoto et al, 2004de Curtis and Gnatkovsky, 2009a,b;and Section 6). Seizure-like events that involve different limbic structures following a 3-minute application of bicuculline methiodide (which presumably caused an approx.…”

Section: Models Of Epileptiform Synchronizationmentioning

confidence: 99%

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

Avoli¹,

Curtis²

2011

Progress in Neurobiology

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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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“…As in ICC, the balance of excitation by NMDA receptors and inhibition due to GABA A receptors is the key mechanism to regulate hippocampal excitability (Dingledine et al 1986). When regulation by GABA synapses is lost, epileptiform bursting occurs (Dingledine et al 1986;Smith 1992;Wagner 1996), and this may be related to pathological seizure activity in both ICC (Smith 1992;Li et al 1994) and the hippocampus (Coulter 2001;Avoli et al 2002;Nadler 2003).…”

Section: Implications For the Regulation Of Firing In The Icc In Vivomentioning

confidence: 99%

Neuronal Responses to Lemniscal Stimulation in Laminar Brain Slices of the Inferior Colliculus

Sivaramakrishnan

Oliver

2005

JARO

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The central nucleus of the inferior colliculus (ICC) receives inputs from all parts of the auditory brainstem and transmits the information to the forebrain. Fibrodendritic laminae of the ICC provide a structural basis for a tonotopic organization, and the interaction of inputs within a single layer is important for ICC processing. Transverse slice planes of the ICC sever the layers and many of the ascending axons that enter through the lateral lemniscus. Consequently, the activity initiated within a lamina by a pure lemniscal stimulus is not well characterized. Here, we use a slice plane that maintains the integrity of the laminae in ICC and allows the axons in the lateral lemniscus to be stimulated at a distance from the ICC. We examined both the postsynaptic currents and potentials of the same neurons to lemniscal stimuli in this laminar brain slice. Our main finding is that lemniscal stimulation evokes prolonged synaptic potentials in ICC neurons. Synaptic potential amplitudes and durations increase with lemniscal shock strength. In õ50% of ICC neurons, the postsynaptic potential is equal in duration to the postsynaptic current, whereas in the remaining neurons it is three to four times longer. Synaptic responses to single shocks or shock trains exhibit plateau potentials that enable sustained firing in ICC neurons. Plateau potentials are evoked by N-methyl-D-aspartate (NMDA) receptor activation, and their amplitudes and durations are regulated by both NMDA-R and gamma-aminobutyric acid A (GABA A )-R activation. These data suggest that in the intact laminae of the ICC, lemniscal inputs initiate sustained firing through monosynaptic and polysynaptic NMDA-mediated synapses regulated by GABA A synapses.

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Network and pharmacological mechanisms leading to epileptiform synchronization in the limbic system in vitro

Cited by 410 publications

References 226 publications

Glutamatergic pre-ictal discharges emerge at the transition to seizure in human epilepsy

Glutamatergic pre-ictal discharges emerge at the transition to seizure in human epilepsy

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

Neuronal Responses to Lemniscal Stimulation in Laminar Brain Slices of the Inferior Colliculus

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