Back to Search Start Over

Low frequency stimulation for seizure suppression: Identification of optimal targets in the entorhinal-hippocampal circuit.

Authors :
Kleis P
Paschen E
Häussler U
Haas CA
Source :
Brain stimulation [Brain Stimul] 2024 Mar-Apr; Vol. 17 (2), pp. 395-404. Date of Electronic Publication: 2024 Mar 24.
Publication Year :
2024

Abstract

Background: Mesial temporal lobe epilepsy (MTLE) with hippocampal sclerosis (HS) is a common form of drug-resistant focal epilepsy in adults. Treatment for pharmacoresistant patients remains a challenge, with deep brain stimulation (DBS) showing promise for alleviating intractable seizures. This study explores the efficacy of low frequency stimulation (LFS) on specific neuronal targets within the entorhinal-hippocampal circuit in a mouse model of MTLE.<br />Objective: Our previous research demonstrated that LFS of the medial perforant path (MPP) fibers in the sclerotic hippocampus reduced seizures in epileptic mice. Here, we aimed to identify the critical neuronal population responsible for this antiepileptic effect by optogenetically stimulating presynaptic and postsynaptic compartments of the MPP-dentate granule cell (DGC) synapse at 1 Hz. We hypothesize that specific targets for LFS can differentially influence seizure activity depending on the cellular identity and location within or outside the seizure focus.<br />Methods: We utilized the intrahippocampal kainate (ihKA) mouse model of MTLE and targeted specific neural populations using optogenetic stimulation. We recorded intracranial neuronal activity from freely moving chronically epileptic mice with and without optogenetic LFS up to 3 h.<br />Results: We found that LFS of MPP fibers in the sclerotic hippocampus effectively suppressed epileptiform activity while stimulating principal cells in the MEC had no impact. Targeting DGCs in the sclerotic septal or non-sclerotic temporal hippocampus with LFS did not reduce seizure numbers but shortened the epileptiform bursts.<br />Conclusion: Presynaptic stimulation of the MPP-DGC synapse within the sclerotic hippocampus is critical for seizure suppression via LFS.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1876-4754
Volume :
17
Issue :
2
Database :
MEDLINE
Journal :
Brain stimulation
Publication Type :
Academic Journal
Accession number :
38531502
Full Text :
https://doi.org/10.1016/j.brs.2024.03.017