Optogenetically induced seizure and the longitudinal hippocampal network dynamics
Open accessAbstract
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.
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Hippocampal hyper-excitability is a paroxysmal and self-limited neuronal network phenomenon characterized by the hyper-synchrony of a large population of neurons.
“Hippocampal hyper-excitability represents a paroxysmal and self-limited neuronal network phenomenon characterized by the hyper-synchrony of a large population of neurons [51]”
From Hippocampal neuro-networks and dendritic spine perturbations in epileptogenesis are attenuated by neuroprotectin D1 (2015) · cites this paper as [51]
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- Authors
- Osawa, S.-I., Iwasaki, M., Hosaka, R., Matsuzaka, Y., Tomita, H., Ishizuka, T., Sugano, E., Okumura, E., Yawo, H., Nakasato, N., Tominaga, T., & Mushiake, H.
- Affiliations
- Tohoku University (JP)
- Fukuoka University (JP)
- Iwate University (JP)
- Corresponding author
- Iwasaki, Masaki
- ORCID
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2013-04-10
- Volume
- 8
- Issue
- 4
- Pages
- e60928
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3622611
- OpenAlex
- W2064139020
- Cited by
- 96
- References
- 51
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 4 · 2023: 17 · 2022: 3 · 2021: 11 · 2020: 9 · 2019: 8 · 2018: 7 · 2017: 4 · 2016: 5 · 2015: 11 · 2014: 6 · 2013: 1
- FWCI
- 5.45
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (acceptedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Iwate University Repository (Iwate University) (submittedVersion, cc-by-nc-nd)
- Funders
- Japan Epilepsy Research Foundation
- Epilepsiatutkimussäätiö
- Japan Society for the Promotion of Science (25115701, 22300124, 25250001, 25670103, 23659681)
- Japan Science and Technology Agency (CREST)
- Core Research for Evolutional Science and Technology
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural dynamics and brain function
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- hippocampus, channelrhodopsin-2, local field potentials, Granger causality, signal flow, c-fos, seizure dynamics, epilepsy, hippocampal network dynamics
- MeSH terms
- Dependovirus, Animals, Genetic Vectors, Hippocampus, Seizures, Rats, Rats, Transgenic
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