Hippocampal low-frequency stimulation prevents seizure generation in a mouse model of mesial temporal lobe epilepsy
- Medical Center - University of Freiburg, Faculty of Medicine, Germany
- University of Freiburg, Germany
- Faculty of Engineering, University of Freiburg, Germany
Abstract
Mesial temporal lobe epilepsy (MTLE) is the most common form of focal, pharmacoresistant epilepsy in adults and is often associated with hippocampal sclerosis. Here, we established the efficacy of optogenetic and electrical low-frequency stimulation (LFS) in interfering with seizure generation in a mouse model of MTLE. Specifically, we applied LFS in the sclerotic hippocampus to study the effects on spontaneous subclinical and evoked generalized seizures. We found that stimulation at 1 Hz for one hour resulted in an almost complete suppression of spontaneous seizures in both hippocampi. This seizure-suppressive action during daily stimulation remained stable over several weeks. Furthermore, LFS for 30 min before a pro-convulsive stimulus successfully prevented seizure generalization. Finally, acute slice experiments revealed a reduced efficacy of perforant path transmission onto granule cells upon LFS. Taken together, our results suggest that hippocampal LFS constitutes a promising approach for seizure control in MTLE.
Data availability
The LFP dataset is available on Open Science Framework: https://osf.io/uk94m/. The source code files for the seizure detection algorithm is accessible at Zenodo (DOI: 10.5281/zenodo.4110614). The source code for the seizure detection algorithm (Heining et al., 2019) was developed using previously published LFP data (Froriep et al., 2012; Janz et al., 2017b).
-
Hippocampal low-frequency stimulation prevents seizure generation in a mouse model of mesial temporal lobe epilepsyOpen Science Framework, DOI 10.17605/OSF.IO/UK94M.
Article and author information
Author details
Funding
Deutsche Forschungsgemeinschaft (EXC 1086)
- Ute Häussler
- Marlene Bartos
- Ulrich Egert
- Carola A Haas
Deutsche Forschungsgemeinschaft (HA 1443/11-1)
- Carola A Haas
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- John R Huguenard, Stanford University School of Medicine, United States
Ethics
Animal experimentation: All animal procedures were carried out in accordance with the guidelines of the European Community's Council Directive of 22 September 2010 (2010/63/EU) and were approved by the regional council (Regierungspräsidium Freiburg).
Version history
- Received: December 17, 2019
- Accepted: December 13, 2020
- Accepted Manuscript published: December 22, 2020 (version 1)
- Version of Record published: January 11, 2021 (version 2)
Copyright
© 2020, Paschen et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 4,421
- views
-
- 513
- downloads
-
- 37
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Hippocampal low-frequency stimulation prevents seizure generation in a mouse model of mesial temporal lobe epilepsy
eLife 9:e54518.
https://doi.org/10.7554/eLife.54518
Further reading
-
- Genetics and Genomics
- Neuroscience
Single-cell RNA sequencing reveals the extent to which marmosets carry genetically distinct cells from their siblings.
-
- Neuroscience
We are unresponsive during slow-wave sleep but continue monitoring external events for survival. Our brain wakens us when danger is imminent. If events are non-threatening, our brain might store them for later consideration to improve decision-making. To test this hypothesis, we examined whether novel vocabulary consisting of simultaneously played pseudowords and translation words are encoded/stored during sleep, and which neural-electrical events facilitate encoding/storage. An algorithm for brain-state-dependent stimulation selectively targeted word pairs to slow-wave peaks or troughs. Retrieval tests were given 12 and 36 hr later. These tests required decisions regarding the semantic category of previously sleep-played pseudowords. The sleep-played vocabulary influenced awake decision-making 36 hr later, if targeted to troughs. The words’ linguistic processing raised neural complexity. The words’ semantic-associative encoding was supported by increased theta power during the ensuing peak. Fast-spindle power ramped up during a second peak likely aiding consolidation. Hence, new vocabulary played during slow-wave sleep was stored and influenced decision-making days later.
