title: Optogenetically induced seizure and the longitudinal hippocampal network dynamics.
abstract: Epileptic seizure is a paroxysmal and self-limited phenomenon characterized by abnormal hypersynchrony of a large population of neurons. However, our current understanding of seizure dynamics is still limited. Here we propose a novel in vivo model of seizure-like afterdischarges using optogenetics, and report on investigation of directional network dynamics during seizure along the septo-temporal (ST) axis of hippocampus. Repetitive pulse photostimulation was applied to the rodent hippocampus, in which channelrhodopsin-2 (ChR2) was expressed, under simultaneous recording of local field potentials (LFPs). Seizure-like afterdischarges were successfully induced after the stimulation in both W-TChR2V4 transgenic (ChR2V-TG) rats and in wild type rats transfected with adeno-associated virus (AAV) vectors carrying ChR2. Pulse frequency at 10 and 20 Hz, and a 0.05 duty ratio were optimal for afterdischarge induction. Immunohistochemical c-Fos staining after a single induced afterdischarge confirmed neuronal activation of the entire hippocampus. LFPs were recorded during seizure-like afterdischarges with a multi-contact array electrode inserted along the ST axis of hippocampus. Granger causality analysis of the LFPs showed a bidirectional but asymmetric increase in signal flow along the ST direction. State space presentation of the causality and coherence revealed three discrete states of the seizure-like afterdischarge phenomenon: 1) resting state; 2) afterdischarge initiation with moderate coherence and dominant septal-to-temporal causality; and 3) afterdischarge termination with increased coherence and dominant temporal-to-septal causality. A novel in vivo model of seizure-like afterdischarge was developed using optogenetics, which was advantageous in its reproducibility and artifact-free electrophysiological observations. Our results provide additional evidence for the potential role of hippocampal septo-temporal interactions in seizure dynamics in vivo. Bidirectional networks work hierarchically along the ST hippocampus in the genesis and termination of epileptic seizures.
authors.affiliation: Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Osawa
authors.forename: Masaki
authors.initials: M
authors.lastname: Iwasaki
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Hosaka
authors.forename: Yoshiya
authors.initials: Y
authors.lastname: Matsuzaka
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tomita
authors.forename: Toru
authors.initials: T
authors.lastname: Ishizuka
authors.forename: Eriko
authors.initials: E
authors.lastname: Sugano
authors.forename: Eiichi
authors.initials: E
authors.lastname: Okumura
authors.forename: Hiromu
authors.initials: H
authors.lastname: Yawo
authors.forename: Nobukazu
authors.initials: N
authors.lastname: Nakasato
authors.forename: Teiji
authors.initials: T
authors.lastname: Tominaga
authors.forename: Hajime
authors.initials: H
authors.lastname: Mushiake
mesh_terms: D000818:Animals; D000229:Dependovirus / Q000235:genetics; D005822:Genetic Vectors; D006624:Hippocampus / Q000503:physiopathology*; D051381:Rats; D055647:Rats, Transgenic; D012640:Seizures / Q000235:genetics* / Q000503:physiopathology