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Nat Commun. 2016 Mar 21;7:10962. doi: 10.1038/ncomms10962.

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

Author information

1
Shenzhen Key Lab of Neuropsychiatric Modulation and Collaborative Innovation Center for Brain Science, CAS Center for Excellence in Brain Science and Intelligence Technology, the Brain Cognition and Brain Disease Institute (BCBDI) for Collaboration Research of SIAT at CAS and the McGovern Institute at MIT, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China.
2
University of Chinese Academy of Sciences, Beijing 100049, China.
3
McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, MIT, Cambridge, Massachusetts 02139, USA.

Abstract

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.

PMID:
26997093
PMCID:
PMC4802168
DOI:
10.1038/ncomms10962
[Indexed for MEDLINE]
Free PMC Article

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