Format

Send to

Choose Destination
Exp Neurol. 2015 Jul;269:120-32. doi: 10.1016/j.expneurol.2015.04.001. Epub 2015 Apr 8.

Seizure reduction through interneuron-mediated entrainment using low frequency optical stimulation.

Author information

1
Department of Biomedical Engineering, Neural Engineering Center, Case Western Reserve University, Cleveland OH 44106, USA.
2
Department of Biomedical Engineering, Neural Engineering Center, Case Western Reserve University, Cleveland OH 44106, USA. Electronic address: dominique.durand@case.edu.

Abstract

Low frequency electrical stimulation (LFS) can reduce neural excitability and suppress seizures in animals and patients with epilepsy. However the therapeutic outcome could benefit from the determination of the cell types involved in seizure suppression. We used optogenetic techniques to investigate the role of interneurons in LFS (1Hz) in the epileptogenic hippocampus. Optical low frequency stimulation (oLFS) was first used to activate the cation channel channelrhodopsin-2 (ChR2) in the Thy1-ChR2 transgenic mouse that expresses ChR2 in both excitatory and inhibitory neurons. We found that oLFS could effectively reduce epileptiform activity in the hippocampus through the activation of GAD-expressing hippocampal interneurons. This was confirmed using the VGAT-ChR2 transgenic mouse, allowing for selective optical activation of only GABA interneurons. Activating hippocampal interneurons through oLFS was found to cause entrainment of neural activity similar to electrical stimulation, but through a GABAA-mediated mechanism. These results confirm the robustness of the LFS paradigm and indicate that GABA interneurons play an unexpected role of shaping inter-ictal activity to decrease neural excitability in the hippocampus.

KEYWORDS:

GABA interneuron; Low-frequency stimulation; Mesial temporal lobe epilepsy; Optogenetics; Seizure suppression

PMID:
25863022
PMCID:
PMC4446206
DOI:
10.1016/j.expneurol.2015.04.001
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center