Divergent paths to seizure‐like events
Abstract Much debate exists about how the brain transitions into an epileptic seizure. One source of confusion is that there are likely to be critical differences between experimental seizure models. To address this, we have compared the evolving activity patterns in two widely used in vitro models...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2019-10-01
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| Series: | Physiological Reports |
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| Online Access: | https://doi.org/10.14814/phy2.14226 |
| _version_ | 1818146093584613376 |
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| author | Neela K. Codadu Robert T. Graham Richard J. Burman R. Thomas Jackson‐Taylor Joseph V. Raimondo Andrew J. Trevelyan R. Ryley Parrish |
| author_facet | Neela K. Codadu Robert T. Graham Richard J. Burman R. Thomas Jackson‐Taylor Joseph V. Raimondo Andrew J. Trevelyan R. Ryley Parrish |
| author_sort | Neela K. Codadu |
| collection | DOAJ |
| description | Abstract Much debate exists about how the brain transitions into an epileptic seizure. One source of confusion is that there are likely to be critical differences between experimental seizure models. To address this, we have compared the evolving activity patterns in two widely used in vitro models of epileptic discharges. Brain slices from young adult mice were prepared in the same way and bathed either in 0 Mg2+ or 100 µmol/L 4AP artificial cerebrospinal fluid. We have found that while local field potential recordings of epileptiform discharges in the two models appear broadly similar, patch‐clamp analysis reveals an important difference in the relative degree of glutamatergic involvement. 4AP affects parvalbumin‐expressing interneurons more than other cortical populations, destabilizing their resting state and inducing spontaneous bursting behavior. Consequently, the most prominent pattern of transient discharge (“interictal event”) in this model is almost purely GABAergic, although the transition to seizure‐like events (SLEs) involves pyramidal recruitment. In contrast, interictal discharges in 0 Mg2+ are only maintained by a very large glutamatergic component that also involves transient discharges of the interneurons. Seizure‐like events in 0 Mg2+ have significantly higher power in the high gamma frequency band (60–120Hz) than these events do in 4AP, and are greatly delayed in onset by diazepam, unlike 4AP events. We, therefore, conclude that the 0 Mg2+ and 4AP models display fundamentally different levels of glutamatergic drive, demonstrating how ostensibly similar pathological discharges can arise from different sources. We contend that similar interpretative issues will also be relevant to clinical practice. |
| first_indexed | 2024-12-11T12:13:52Z |
| format | Article |
| id | doaj.art-4e551e9cdeed4faaadcabc914c99a425 |
| institution | Directory Open Access Journal |
| issn | 2051-817X |
| language | English |
| last_indexed | 2024-12-11T12:13:52Z |
| publishDate | 2019-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Physiological Reports |
| spelling | doaj.art-4e551e9cdeed4faaadcabc914c99a4252022-12-22T01:07:43ZengWileyPhysiological Reports2051-817X2019-10-01719n/an/a10.14814/phy2.14226Divergent paths to seizure‐like eventsNeela K. Codadu0Robert T. Graham1Richard J. Burman2R. Thomas Jackson‐Taylor3Joseph V. Raimondo4Andrew J. Trevelyan5R. Ryley Parrish6Institute of Neuroscience Medical School Newcastle University Newcastle upon Tyne United KingdomInstitute of Neuroscience Medical School Newcastle University Newcastle upon Tyne United KingdomDivision of Cell Biology Department of Human Biology, Neuroscience Institute and Institute of Infectious Disease and Molecular Medicine Faculty of Health Sciences University of Cape Town Cape Town South AfricaInstitute of Neuroscience Medical School Newcastle University Newcastle upon Tyne United KingdomDivision of Cell Biology Department of Human Biology, Neuroscience Institute and Institute of Infectious Disease and Molecular Medicine Faculty of Health Sciences University of Cape Town Cape Town South AfricaInstitute of Neuroscience Medical School Newcastle University Newcastle upon Tyne United KingdomInstitute of Neuroscience Medical School Newcastle University Newcastle upon Tyne United KingdomAbstract Much debate exists about how the brain transitions into an epileptic seizure. One source of confusion is that there are likely to be critical differences between experimental seizure models. To address this, we have compared the evolving activity patterns in two widely used in vitro models of epileptic discharges. Brain slices from young adult mice were prepared in the same way and bathed either in 0 Mg2+ or 100 µmol/L 4AP artificial cerebrospinal fluid. We have found that while local field potential recordings of epileptiform discharges in the two models appear broadly similar, patch‐clamp analysis reveals an important difference in the relative degree of glutamatergic involvement. 4AP affects parvalbumin‐expressing interneurons more than other cortical populations, destabilizing their resting state and inducing spontaneous bursting behavior. Consequently, the most prominent pattern of transient discharge (“interictal event”) in this model is almost purely GABAergic, although the transition to seizure‐like events (SLEs) involves pyramidal recruitment. In contrast, interictal discharges in 0 Mg2+ are only maintained by a very large glutamatergic component that also involves transient discharges of the interneurons. Seizure‐like events in 0 Mg2+ have significantly higher power in the high gamma frequency band (60–120Hz) than these events do in 4AP, and are greatly delayed in onset by diazepam, unlike 4AP events. We, therefore, conclude that the 0 Mg2+ and 4AP models display fundamentally different levels of glutamatergic drive, demonstrating how ostensibly similar pathological discharges can arise from different sources. We contend that similar interpretative issues will also be relevant to clinical practice.https://doi.org/10.14814/phy2.14226Epilepsyictal eventsinterneuronsinterictal events |
| spellingShingle | Neela K. Codadu Robert T. Graham Richard J. Burman R. Thomas Jackson‐Taylor Joseph V. Raimondo Andrew J. Trevelyan R. Ryley Parrish Divergent paths to seizure‐like events Physiological Reports Epilepsy ictal events interneurons interictal events |
| title | Divergent paths to seizure‐like events |
| title_full | Divergent paths to seizure‐like events |
| title_fullStr | Divergent paths to seizure‐like events |
| title_full_unstemmed | Divergent paths to seizure‐like events |
| title_short | Divergent paths to seizure‐like events |
| title_sort | divergent paths to seizure like events |
| topic | Epilepsy ictal events interneurons interictal events |
| url | https://doi.org/10.14814/phy2.14226 |
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