The initiation and spread of epileptiform bursts in thein vitro hippocampal slice

Knowles, W. Douglas; Traub, Roger D.; Strowbridge, Ben W.

doi:10.1016/0306-4522(87)90134-5

Cited by 60 publications

(46 citation statements)

References 38 publications

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“…Similar patterns of recruitment leading to initiation have been observed in both hippocampal slices (Wong and Traub, 1983;Knowles et al, 1987), in the developing retina (Feller et al, 1996), and in computational models of both systems (Traub and Wong, 1983b;Traub et al, 1993;Feller et al, 1997;Butts et al, 1999). Waves in disinhibited hippocampal slices initiate exclusively from the CA2 region (Knowles et al, 1987).…”

Section: Data Presented Insupporting

confidence: 63%

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Initiation, Propagation, and Termination of Epileptiform Activity in Rodent NeocortexIn VitroInvolve Distinct Mechanisms

Pinto¹,

Patrick²,

Huang³

et al. 2005

J. Neurosci.

196

173

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Waves of epileptiform activity in neocortex have three phenomenological stages: initiation, propagation, and termination. We use a well studied model of epileptiform activity in vitro to investigate directly the hypothesis that each stage is governed by an independent mechanism within the underlying cortical circuit. Using the partially disinhibited neocortical slice preparation, activity is induced and modulated using neurotransmitter receptor antagonists and is measured using both intracellular recordings and a linear array of extracellular electrodes. We find that initiation depends on both synaptic excitation and inhibition and entails a slow process of recruitment at discrete spatial locations within cortical layer 5 but not layer 2/3. Propagation depends on synaptic excitation but not inhibition and is a fast process that involves neurons across the spatial extent of the slice and in all cortical layers. Termination is modulated by synaptic excitation and inhibition. In space, termination occurs reliably at discrete locations. In time, termination is characterized by a strong depolarizing shift (block) and recovery of neurons in all cortical layers. These results suggest that the phenomenological stages of epileptiform events correspond to distinct mechanistic stages.

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Section: Data Presented Insupporting

confidence: 63%

“…Waves in disinhibited hippocampal slices initiate exclusively from the CA2 region (Knowles et al, 1987). Waves in the developing retina initiate from randomly distributed sites (Feller et al, 1997).…”

Section: Data Presented Inmentioning

confidence: 99%

Initiation, Propagation, and Termination of Epileptiform Activity in Rodent NeocortexIn VitroInvolve Distinct Mechanisms

Pinto¹,

Patrick²,

Huang³

et al. 2005

J. Neurosci.

196

173

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“…First, recurrent EPSPs mediate synchronized discharges of pyramidal cells. Not only is the PDS the product of such interactions, but as suggested previously the synchronized afterdischarges are likely mediated by activation of this same group of recurrent excitatory synapses (Miles et al, 1984;Knowles et al, 1987). Second, there appears to be another form of recurrent excitation that underlies the sustained depolarization of electrographic seizures.…”

Section: Discussionmentioning

confidence: 79%

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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“…Although a site of seizure initiation may be created by local damage, it is not likely that this will occur on penetration of our 33 gm diameter recording electrodes. Knowles et al (1987), who used 61 gm diameter electrodes in CA2-3, found that spontaneous bursts always originated at a discrete focus at or near CA2.…”

Section: Discussionmentioning

confidence: 99%

“…Voskuyl and Albus (1985) found a propagation from CA3 to CA1 at 0.1-0.5 m/s for one type and 0.01 m/s for a second type of spontaneous 4-AP bursts. Schwartzkroin and Prince (1978) reported a velocity of approximately 0.1 m/s in the penicillin model and Knowles et al (1987) found in CA2-3 an average value of 0.13 m/s in the picrotoxin model. In the low calcium model of epilepsy a very slow spread was observed in CA1, at a mean velocity of 0.00174 m/s .…”

Section: Introductionmentioning

confidence: 93%

Propagation velocity of epileptiform activity in the hippocampus

Holsheimer

Silva

1989

Exp Brain Res

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Summary. The propagation of epileptiform burst activity was investigated in the CA1 area of the in-vitro hippocampal slice preparation of the guinea pig. This activity was provoked by 0.1 mM 4-aminopyridine in the bathing medium and was recorded in the pyramidal layer with an array of eight electrodes. The delay between the first population spike of a burst recorded with different electrodes was calculated using the cross-correlation function. The propagation velocity was estimated from the delays and the electrode intervals. It was found that the velocity of spontaneous and evoked epileptiform bursts varies between 0.15 and 5 m/s and is not confined to the range of conduction velocities of the fibre systems in CA 1 (0.3-0.55 and 1.0-1.8 m/s). Different velocities can be present in different parts of the CA1 area and the initiation of spontaneous bursts is not confined to the CA2-3 areas, but can also occur in CA1. Burst activity also propagated in a low calcium-high magnesium medium. Different mechanisms of propagation are discussed and it is argued that the propagation velocity due to ephaptic interaction may vary largely. It is concluded that epileptiform activity can be propagated not only by synaptic connections at or near the pyramidal layer, but also by way of electrical field effects of population spikes.

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The initiation and spread of epileptiform bursts in thein vitro hippocampal slice

Cited by 60 publications

References 38 publications

Initiation, Propagation, and Termination of Epileptiform Activity in Rodent NeocortexIn VitroInvolve Distinct Mechanisms

Initiation, Propagation, and Termination of Epileptiform Activity in Rodent NeocortexIn VitroInvolve Distinct Mechanisms

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

Propagation velocity of epileptiform activity in the hippocampus

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