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Seizures initiate in zones of relative hyperexcitation in a zebrafish epilepsy model.

TitleSeizures initiate in zones of relative hyperexcitation in a zebrafish epilepsy model.
Publication TypeJournal Article
Year of Publication2022
AuthorsNiemeyer JE, Gadamsetty P, Chun C, Sylvester S, Lucas JP, Ma H, Schwartz TH, Aksay ERF
JournalBrain
Date Published2022 Feb 23
ISSN1460-2156
Abstract

Seizures are thought to arise from an imbalance of excitatory and inhibitory neuronal activity. While most classical studies suggest excessive excitatory neural activity plays a generative role, some recent findings challenge this view and instead argue that excessive activity in inhibitory neurons initiates seizures. We investigated this question of imbalance in a zebrafish seizure model with two-photon imaging of excitatory and inhibitory neuronal activity throughout the brain using a nuclear-localized calcium sensor. We found that seizures consistently initiated in circumscribed zones of the midbrain before propagating to other brain regions. Excitatory neurons were both more prevalent and more likely to be recruited than inhibitory neurons in initiation as compared with propagation zones. These findings support a mechanistic picture whereby seizures initiate in a region of hyper-excitation, then propagate more broadly once inhibitory restraint in the surround is overcome.

DOI10.1093/brain/awac073
Alternate JournalBrain
PubMed ID35196385