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Nat Commun DOI:10.1038/ncomms10962

Optogenetic dissection of ictal propagation in the hippocampal-entorhinal cortex structures.

Publication TypeJournal Article
Year of Publication2016
AuthorsLu, Y, Zhong, C, Wang, L, Wei, P, He, W, Huang, K, Zhang, Y, Zhan, Y, Feng, G, Wang, L
JournalNat Commun
Date Published2016 Mar 21
KeywordsAction Potentials, Animals, Dentate Gyrus, Entorhinal Cortex, gamma-Aminobutyric Acid, Hippocampus, Interneurons, Mice, Optogenetics, Proto-Oncogene Proteins c-fos, Seizures

Temporal lobe epilepsy (TLE) is one of the most common drug-resistant forms of epilepsy in adults and usually originates in the hippocampal formations. However, both the network mechanisms that support the seizure spread and the exact directions of ictal propagation remain largely unknown. Here we report the dissection of ictal propagation in the hippocampal-entorhinal cortex (HP-EC) structures using optogenetic methods in multiple brain regions of a kainic acid-induced model of TLE in VGAT-ChR2 transgenic mice. We perform highly temporally precise cross-area analyses of epileptic neuronal networks and find a feed-forward propagation pathway of ictal discharges from the dentate gyrus/hilus (DGH) to the medial entorhinal cortex, instead of a re-entrant loop. We also demonstrate that activating DGH GABAergic interneurons can significantly inhibit the spread of ictal seizures and largely rescue behavioural deficits in kainate-exposed animals. These findings may shed light on future therapeutic treatments of TLE.


Alternate JournalNat Commun
PubMed ID26997093
PubMed Central IDPMC4802168