title: Optogenetic dissection of ictal propagation in the hippocampal-entorhinal cortex structures.
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.
authors.affiliation: 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.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
authors.affiliation: 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.|University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhong
authors.affiliation: 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.|University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Lulu
authors.initials: L
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Wei
authors.affiliation: 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.
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.affiliation: 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.|University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Kang
authors.initials: K
authors.lastname: Huang
authors.affiliation: 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.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhan
authors.affiliation: McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, MIT, Cambridge, Massachusetts 02139, USA.
authors.forename: Guoping
authors.initials: G
authors.lastname: Feng
authors.affiliation: 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.
authors.forename: Liping
authors.initials: L
authors.lastname: Wang
mesh_terms: D000200:Action Potentials; D000818:Animals; D018891:Dentate Gyrus / Q000503:physiopathology; D018728:Entorhinal Cortex / Q000503:physiopathology*; D006624:Hippocampus / Q000503:physiopathology*; D007395:Interneurons / Q000378:metabolism; D051379:Mice; D062308:Optogenetics / Q000379:methods*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D012640:Seizures / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D005680:gamma-Aminobutyric Acid