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Ripple-related firing of identified deep CA1 pyramidal cells in chronic temporal lobe epilepsy in mice.

ABSTRACT: Objective:Temporal lobe epilepsy (TLE) is often associated with memory deficits. Reactivation of memory traces in the hippocampus occurs during sharp-wave ripples (SWRs; 140-250 Hz). To better understand the mechanisms underlying high-frequency oscillations and cognitive comorbidities in epilepsy, we evaluated how rigorously identified deep CA1 pyramidal cells (dPCs) discharge during SWRs in control and TLE mice. Methods:We used the unilateral intraamygdala kainate model of TLE in video-electroencephalography (EEG) verified chronically epileptic adult mice. Local field potential and single-cell recordings were performed using juxtacellular recordings from awake control and TLE mice resting on a spherical treadmill, followed by post hoc identification of the recorded cells. Results:Hippocampal SWRs in TLE mice occurred with increased intraripple frequency compared to control mice. The frequency of SWR events was decreased, whereas the overall frequency of SWRs, interictal epileptiform discharges, and high-frequency ripples (250-500 Hz) together was not altered. CA1 dPCs in TLE mice showed significantly increased firing during ripples as well as between the ripple events. The strength of ripple modulation of dPC discharges increased in TLE without alteration of the preferred phase of firing during the ripple waves. Significance:These juxtacellular electrophysiology data obtained from identified CA1 dPCs from chronically epileptic mice are in general agreement with recent findings indicating distortion of normal firing patterns during offline SWRs as a mechanism underlying deficits in memory consolidation in epilepsy. Because the primary seizure focus in our experiments was in the amygdala and we recorded from the CA1 region, these results are also in agreement with the presence of altered high-frequency oscillations in areas of secondary seizure spread.

SUBMITTER: Marchionni I

PROVIDER: S-EPMC6546014 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Ripple-related firing of identified deep CA1 pyramidal cells in chronic temporal lobe epilepsy in mice.

Marchionni Ivan I Oberoi Michelle M Soltesz Ivan I Alexander Allyson A

Epilepsia open 20190304 2

<h4>Objective</h4>Temporal lobe epilepsy (TLE) is often associated with memory deficits. Reactivation of memory traces in the hippocampus occurs during sharp-wave ripples (SWRs; 140-250 Hz). To better understand the mechanisms underlying high-frequency oscillations and cognitive comorbidities in epilepsy, we evaluated how rigorously identified deep CA1 pyramidal cells (dPCs) discharge during SWRs in control and TLE mice.<h4>Methods</h4>We used the unilateral intraamygdala kainate model of TLE in ...[more]

PMID: 31168492

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Project description:ObjectivePatients with suspected mesial temporal lobe (MTL) epilepsy typically undergo inpatient video-electroencephalography (EEG) monitoring with scalp and/or intracranial electrodes for 1 to 2 weeks to localize and lateralize the seizure focus or foci. Chronic ambulatory electrocorticography (ECoG) in patients with MTL epilepsy may provide additional information about seizure lateralization. This analysis describes data obtained from chronic ambulatory ECoG in patients with suspected bilateral MTL epilepsy in order to assess the time required to determine the seizure lateralization and whether this information could influence treatment decisions.MethodsAmbulatory ECoG was reviewed in patients with suspected bilateral MTL epilepsy who were among a larger cohort with intractable epilepsy participating in a randomized controlled trial of responsive neurostimulation. Subjects were implanted with bilateral MTL leads and a cranially implanted neurostimulator programmed to detect abnormal interictal and ictal ECoG activity. ECoG data stored by the neurostimulator were reviewed to determine the lateralization of electrographic seizures and the interval of time until independent bilateral MTL electrographic seizures were recorded.ResultsEighty-two subjects were implanted with bilateral MTL leads and followed for 4.7 years on average (median 4.9 years). Independent bilateral MTL electrographic seizures were recorded in 84%. The average time to record bilateral electrographic seizures in the ambulatory setting was 41.6 days (median 13 days, range 0-376 days). Sixteen percent had only unilateral electrographic seizures after an average of 4.6 years of recording.SignificanceAbout one third of the subjects implanted with bilateral MTL electrodes required >1 month of chronic ambulatory ECoG before the first contralateral MTL electrographic seizure was recorded. Some patients with suspected bilateral MTL seizures had only unilateral electrographic seizures. Chronic ambulatory ECoG in patients with suspected bilateral MTL seizures provides data in a naturalistic setting, may complement data from inpatient video-EEG monitoring, and can contribute to treatment decisions.

Dataset Information

Ripple-related firing of identified deep CA1 pyramidal cells in chronic temporal lobe epilepsy in mice.

Publications

Ripple-related firing of identified deep CA1 pyramidal cells in chronic temporal lobe epilepsy in mice.

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