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

First Author  Ladas TP Year  2015
Journal  Exp Neurol Volume  269
Pages  120-32 PubMed ID  25863022
Mgi Jnum  J:225462 Mgi Id  MGI:5693339
Doi  10.1016/j.expneurol.2015.04.001 Citation  Ladas TP, et al. (2015) Seizure reduction through interneuron-mediated entrainment using low frequency optical stimulation. Exp Neurol 269:120-32
abstractText  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.
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