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Epileptic seizure is a paroxysmal and self-limited phenomenon characterized by abnormal hypersynchrony of a largepopulation of neurons. However, our current understanding of seizure dynamics is still limited. Here we propose a novel invivo model of seizure-like afterdischarges using optogenetics, and report on investigation of directional network dynamicsduring seizure along the septo-temporal (ST) axis of hippocampus. Repetitive pulse photostimulation was applied to therodent hippocampus, in which channelrhodopsin-2 (ChR2) was expressed, under simultaneous recording of local fieldpotentials (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 frequencyat 10 and 20 Hz, and a 0.05 duty ratio were optimal for afterdischarge induction. Immunohistochemical c-Fos staining aftera single induced afterdischarge confirmed neuronal activation of the entire hippocampus. LFPs were recorded duringseizure-like afterdischarges with a multi-contact array electrode inserted along the ST axis of hippocampus. Grangercausality analysis of the LFPs showed a bidirectional but asymmetric increase in signal flow along the ST direction. Statespace presentation of the causality and coherence revealed three discrete states of the seizure-like afterdischargephenomenon: 1) resting state; 2) afterdischarge initiation with moderate coherence and dominant septal-to-temporalcausality; and 3) afterdischarge termination with increased coherence and dominant temporal-to-septal causality. A novel invivo model of seizure-like afterdischarge was developed using optogenetics, which was advantageous in its reproducibilityand artifact-free electrophysiological observations. Our results provide additional evidence for the potential role ofhippocampal septo-temporal interactions in seizure dynamics in vivo. Bidirectional networks work hierarchically along theST hippocampus in the genesis and termination of epileptic seizures.



    PLOS ONE 8(4), e60928, 2013-04-01

    Public Library of Science


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