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Role of inhibitory control in modulating focal seizure spread.

TitleRole of inhibitory control in modulating focal seizure spread.
Publication TypeJournal Article
Year of Publication2018
AuthorsLiou J-Y, Ma H, Wenzel M, Zhao M, Baird-Daniel E, Smith EH, Daniel A, Emerson R, Yuste R, Schwartz TH, Schevon CA
JournalBrain
Volume141
Issue7
Pagination2083-2097
Date Published2018 07 01
ISSN1460-2156
Keywords4-Aminopyridine, Animals, Calcium, Electric Stimulation, Electroencephalography, Epilepsy, Interneurons, Male, Nerve Net, Neural Pathways, Neurons, Rats, Rats, Sprague-Dawley, Seizures, Synaptic Transmission
Abstract

Focal seizure propagation is classically thought to be spatially contiguous. However, distribution of seizures through a large-scale epileptic network has been theorized. Here, we used a multielectrode array, wide field calcium imaging, and two-photon calcium imaging to study focal seizure propagation pathways in an acute rodent neocortical 4-aminopyridine model. Although ictal neuronal bursts did not propagate beyond a 2-3-mm region, they were associated with hemisphere-wide field potential fluctuations and parvalbumin-positive interneuron activity outside the seizure focus. While bicuculline surface application enhanced contiguous seizure propagation, focal bicuculline microinjection at sites distant to the 4-aminopyridine focus resulted in epileptic network formation with maximal activity at the two foci. Our study suggests that both classical and epileptic network propagation can arise from localized inhibition defects, and that the network appearance can arise in the context of normal brain structure without requirement for pathological connectivity changes between sites.

DOI10.1093/brain/awy116
Alternate JournalBrain
PubMed ID29757347
PubMed Central IDPMC6022627
Grant ListR01 NS095368 / NS / NINDS NIH HHS / United States
R01 NS084142 / NS / NINDS NIH HHS / United States
R01 MH100561 / MH / NIMH NIH HHS / United States
R01 EY011787 / EY / NEI NIH HHS / United States
DP1 EY024503 / EY / NEI NIH HHS / United States
R01 MH101218 / MH / NIMH NIH HHS / United States