Intracellular phenomena and spread of epileptic seizure discharges

Sawa, Masaichi; Nakamura, Kyugo; Naito, Haruhiko

doi:10.1016/0013-4694(68)90120-x

Cited by 40 publications

(5 citation statements)

References 15 publications

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“…In particular, it has been hypothesized 7 that such heterogeneity could reflect three main sequential stages or states during seizure spreading: ‘depressed’, ‘projected’ and ‘propagated’ states. The fact that the heterogeneity reported here in human epilepsy appears simultaneously in small patches of neocortex would speak against this hypothesis; or, alternatively, it would require that different groups of neurons entered and dwelled in different states with different time constants, perhaps owing to differences in initial conditions or in intrinsic and local network dynamical properties.…”

Section: Discussionmentioning

confidence: 99%

Single-neuron dynamics in human focal epilepsy

et al. 2011

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Epileptic seizures are traditionally characterized as the ultimate expression of monolithic, hypersynchronous neuronal activity arising from unbalanced runaway excitation. Here we report the first examination of spike train patterns in large ensembles of single neurons during seizures in persons with epilepsy. Contrary to the traditional view, neuronal spiking activity during seizure initiation and spread was highly heterogeneous, not hypersynchronous, suggesting complex interactions among different neuronal groups even at the spatial scale of small cortical patches. In contrast to earlier stages, seizure termination is a nearly homogenous phenomenon followed by an almost complete cessation of spiking across recorded neuronal ensembles. Notably, even neurons outside the region of seizure onset showed significant changes in activity minutes before the seizure. These findings suggest a revision of current thinking about seizure mechanisms and point to the possibility of seizure prevention based on spiking activity in neocortical neurons.

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Section: Discussionmentioning

confidence: 99%

Single-neuron dynamics in human focal epilepsy

et al. 2011

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“…The most cogent arguments against its role were observations that some cells simply did not undergo a slow depolarization, yet underwent rapid repetitive depolarizations during electrographic seizures. Sawa et al (1968) attempted to explain these observations by arguing that during seizures neurons could exist in one of several seizure states. For instance, at a site of seizure initiation (in their experimental model this was thought to be the site in cortex where repetitive electrical stimuli were applied) "generator" neurons were known to undergo a sustained depolarization concurrent with intense repetitive depolarizations.…”

Section: Discussionmentioning

confidence: 99%

“…The significance of the sustained depolarization was debated by early investigators. Some felt that it was essential for seizure generation (Sawa et al, 1968). Others did not (Purpura et al, 1966).…”

mentioning

confidence: 99%

Localized excitatory synaptic interactions mediate the sustained depolarization of electrographic seizures in developing hippocampus

1993

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Repetitive synchronized neuronal discharging that lasts for seconds and even minutes in in vitro brain slice preparations are important new models in experimental epilepsy. In hippocampal slices from 1–2-week- old rats, individual CA3 pyramidal cells undergo a sustained depolarization during such electrographic seizures, induced by GABAA receptor antagonists. In experiments reported here these events were produced in small isolated segments of the CA3 subfield, measuring only 400–500 microns along the cell body layer. In such minisclices local application of either kynurenic acid or 6-cyano-7-nitroquinoxaline-2–3- dione (CNQX) to the proximal basilar dendrites abolished the synchronized discharges of electrographic seizures. Interictal spikes appeared unaffected by this treatment. Application of these excitatory amino acid receptor antagonists to distal basilar dendrites or apical dendrites was ineffective. In “larger” minislices, measuring 700–1000 microns along the cell body layer, application of kynurenic acid, CNQX, or TTX to the proximal basilar dendrites did not abolish electrographic seizures but instead selectively suppressed the intracellularly recorded sustained depolarization and the coincident slow negative field potential recorded in proximal basilar dendrites. Results of several experiments suggest that electrographic seizures recorded under these conditions were produced by a remote network of “generator cells.” Since the remote neurons were unaffected by local application of the drugs, it seemed likely that they continued to undergo a sustained depolarization. Simultaneous blockade of basilar dendritic synapses in the “generator” population abolished electrographic seizures throughout these larger minislices. These results suggest that the sustained depolarization plays a central role in seizure generation and that it does not have to be generated in every neuron, only in a critical number of “generator cells” for a seizure to occur. Taken together, results presented here suggest that the sustained depolarization of electrographic seizures is a separate physiological process from the more rapid repetitive depolarizations of the seizure discharges and is required if electrographic seizures are to occur. This slow depolarization appears to be synaptically mediated and generated exclusively in proximal basilar dendrites. Therefore, in addition to the excitatory synaptic potentials involved in paroxysmal depolarization shift generation, a second form of recurrent excitation may exist in immature hippocampus. Not only is this physiological process critical for the genesis of seizures, but it also appears to be highly partitioned within the hippocampal laminae.

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“…At some threshold [KIO value, however, the mechanism becomes regenerative and a seizure is initiated. To our knowledge there are eight studies (from six laboratories) of intracellular electrical events during ictal phenomena, using Metrazol-and penicillin-induced seizures, and afterdischarges 12,IS,(26)(27)(28)(29)31). In seven of these studies most neurons had a sustained depolarization of many seconds and many millivolts during the seizure (1,12,IS,(27)(28)(29)31).…”

Section: Discussionmentioning

confidence: 99%

Potassium accumulation in interstitial space during epileptiform seizures

Fertziger¹,

Ranck²

1970

Experimental Neurology

201

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The K4a surface efflux from the cat neocortex and rat hippocampus was studied after preloading with K"a from the surface. This K4s efflux increases from two to nine times during or after all electrically or Metrazol-induced seizures and "spontaneous" seizures. The K4s influx does not change during a seizure, so this increased efflux is not due to change in the diffusion constant or water flow from brain. The time course of the efflux is not compatable with the efflux simply idicating increased turnover of potassium from cells. We conclude there is an increase in the concentration of potassium in the interstitial space during seizures. A model is proposed in which this potassium accumulation is an important step in the regenerative, all-or-none-aspect of the initiation of seizures.

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Intracellular phenomena and spread of epileptic seizure discharges

Cited by 40 publications

References 15 publications

Single-neuron dynamics in human focal epilepsy

Single-neuron dynamics in human focal epilepsy

Localized excitatory synaptic interactions mediate the sustained depolarization of electrographic seizures in developing hippocampus

Potassium accumulation in interstitial space during epileptiform seizures

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