RT Journal Article
SR Electronic
T1 Divergent paths to seizure-like events
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 641530
DO 10.1101/641530
A1 Neela K. Codadu
A1 Robert Graham
A1 Richard J. Burman
A1 R. Thomas Jackson-Taylor
A1 Joseph V. Raimondo
A1 Andrew. J. Trevelyan
A1 R. Ryley Parrish
YR 2019
UL http://biorxiv.org/content/early/2019/05/19/641530.abstract
AB Aim 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 compared the evolving activity patterns in two, widely used, in vitro models of epileptic discharges.Methods We compared brain slices, prepared in the same way from young adult mice, that were bathed either in 0 Mg2+, or 100µM 4AP, artificial cerebrospinal fluid.Results We find 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.Conclusions 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.PVParvalbuminSSTSomatostatinACSFartificial cerebro-spinal fluidSLEseizure-like eventsLRDlate recurrent discharges