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Divergent paths to seizure-like events

Lookup NU author(s): Neela Codadu, Dr Rob Graham, Professor Andrew Trevelyan, Ryley Parrish



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.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.

Publication metadata

Author(s): Codadu NK, Graham RT, Burman RJ, Jackson-Taylor RT, Raimondo JV, Trevelyan AJ, Parrish RR

Publication type: Article

Publication status: Published

Journal: Physiological reports

Year: 2019

Volume: 7

Issue: 19

Print publication date: 06/10/2019

Online publication date: 06/10/2019

Acceptance date: 31/07/2019

Date deposited: 15/10/2019

ISSN (electronic): 2051-817X

Publisher: The Physiological Society


DOI: 10.14814/phy2.14226

PubMed id: 31587522


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Funder referenceFunder name
MR/R005427/1Medical Research Council (MRC)