Hippocampal low-frequency stimulation prevents seizure generation in a mouse model of mesial temporal lobe epilepsy

  1. Enya Paschen  Is a corresponding author
  2. Claudio Elgueta
  3. Katharina Heining
  4. Diego M Vieira
  5. Piret Kleis
  6. Catarina Orcinha
  7. Ute Häussler
  8. Marlene Bartos
  9. Ulrich Egert
  10. Philipp Janz
  11. Carola A Haas  Is a corresponding author
  1. Medical Center - University of Freiburg, Faculty of Medicine, Germany
  2. University of Freiburg, Germany
  3. 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).

The following data sets were generated

Article and author information

Author details

  1. Enya Paschen

    Experimental Epilepsy Research, Dept. of Neurosurgery, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany
    For correspondence
    enya.paschen@uniklinik-freiburg.de
    Competing interests
    The authors declare that no competing interests exist.
  2. Claudio Elgueta

    Institute for Physiology I, University of Freiburg, Freiburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  3. Katharina Heining

    Laboratory for Biomicrotechnology, Dept. of Microsystems Engineering, University of Freiburg, Freiburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  4. Diego M Vieira

    Biomicrotechnology, Dept. of Microsystems Engineering - IMTEK, Faculty of Engineering, University of Freiburg, Freiburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8005-134X
  5. Piret Kleis

    Experimental Epilepsy Research, Dept. of Neurosurgery, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Catarina Orcinha

    Experimental Epilepsy Research, Dept. of Neurosurgery, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  7. Ute Häussler

    Experimental Epilepsy Research, Dept. of Neurosurgery, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  8. Marlene Bartos

    Institute for Physiology I, University of Freiburg, Freiburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9741-1946
  9. Ulrich Egert

    Biomicrotechnology, Dept. of Microsystems Engineering - IMTEK, Faculty of Engineering, University of Freiburg, Freiburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4583-0425
  10. Philipp Janz

    Experimental Epilepsy Research, Dept. of Neurosurgery, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany
    Competing interests
    The authors declare that no competing interests exist.
  11. Carola A Haas

    Experimental Epilepsy Research, Dept. of Neurosurgery, Medical Center - University of Freiburg, Faculty of Medicine, Freiburg, Germany
    For correspondence
    carola.haas@uniklinik-freiburg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7022-4136

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

  1. 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

  1. Received: December 17, 2019
  2. Accepted: December 13, 2020
  3. Accepted Manuscript published: December 22, 2020 (version 1)
  4. 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.

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  1. Enya Paschen
  2. Claudio Elgueta
  3. Katharina Heining
  4. Diego M Vieira
  5. Piret Kleis
  6. Catarina Orcinha
  7. Ute Häussler
  8. Marlene Bartos
  9. Ulrich Egert
  10. Philipp Janz
  11. Carola A Haas
(2020)
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

Share this article

https://doi.org/10.7554/eLife.54518

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