Optogenetically induced seizure and the longitudinal hippocampal network dynamics

• Published in: PloS one 2013-04, Vol.8 (4), p.e60928-e60928
• Main Authors: Osawa, Shin-Ichiro, Iwasaki, Masaki, Hosaka, Ryosuke, Matsuzaka, Yoshiya, Tomita, Hiroshi, Ishizuka, Toru, Sugano, Eriko, Okumura, Eiichi, Yawo, Hiromu, Nakasato, Nobukazu, Tominaga, Teiji, Mushiake, Hajime
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Bioengineering; Biology; Brain; Brain research; c-Fos protein; Coherence; Dependovirus - genetics; Developmental biology; Disease; Dynamics; Engineering; Epilepsy; Experiments; Fos protein; Genetic engineering; Genetic Vectors; Genetics; Hippocampus; Hippocampus - physiopathology; In vivo methods and tests; Information processing; Life sciences; Mathematical analysis; Mathematics; Medicine; Neurons; Neurosciences; Neurosurgery; Optics; Optimization techniques; Physiology; Propagation; Rats; Rats, Transgenic; Reproducibility; Rodents; Seizing; Seizures; Seizures (Medicine); Seizures - genetics; Seizures - physiopathology; University graduates; Viruses
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0060928

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.