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Direct-current Stimulation and Multi-electrode Array Recording of Seizure-like Activity in Mice Brain Slice Preparation
Published on: June 7, 2016
Long-lasting hyperpolarization underlies seizure reduction by low frequency deep brain electrical stimulation
Sheela Toprani1, Dominique M Durand
1D. M. Durand: Neural Engineering Center, Departments of Biomedical Engineering and Neurosciences, Case Western Reserve University, Cleveland, OH 44106, USA. dxd6@case.edu.
The Journal of Physiology
|August 29, 2013
Summary
Low-frequency electrical stimulation (LFS) of the ventral hippocampal commissure (VHC) effectively reduces seizures in mesial temporal lobe epilepsy (MTLE). This seizure reduction is mediated by long-lasting hyperpolarization through GABA(B) inhibitory post-synaptic potentials and slow after-hyperpolarizations.
Area of Science:
- Neuroscience
- Epilepsy Research
- Neurological Disorders
Background:
- Mesial temporal lobe epilepsy (MTLE) is a common neurological condition often resistant to medication.
- Deep brain electrical stimulation (DBS) of grey matter has shown limited success for MTLE.
- Stimulating the ventral hippocampal commissure (VHC) white matter tract with low frequencies (LFS) shows promise for MTLE treatment.
Purpose of the Study:
- To elucidate the mechanisms underlying seizure reduction by LFS of the VHC.
- To investigate the role of stimulus-induced long-lasting hyperpolarization (LLH) in reducing epileptic activity.
- To test the hypothesis that LLH, mediated by GABA(B) inhibitory post-synaptic potentials (IPSPs) and slow after-hyperpolarizations (sAHP), is key to VHC stimulation efficacy.
Main Methods:
- Utilized an in vitro slice preparation of bilateral hippocampi connected by the VHC.
- Applied LFS to the VHC and measured stimulus-induced hyperpolarization using electrophysiology.
- Investigated the role of GABA(B) IPSPs and sAHP by using antagonists to block these pathways.
Main Results:
- LFS of the VHC significantly reduced bilateral hippocampal seizure activity.
- Antagonizing GABA(B) IPSPs or sAHP diminished both stimulus-induced hyperpolarization and LFS efficacy.
- Simultaneous blockade of both GABA(B) IPSPs and sAHP completely abolished the seizure reduction effect of VHC stimulation.
Conclusions:
- LFS of the VHC is an effective strategy for reducing bilateral hippocampal seizures.
- The efficacy of LFS in seizure reduction is dependent on long-lasting hyperpolarization mediated by GABA(B) IPSPs and sAHP.
- Optimizing LFS timing and understanding LLH mechanisms could improve DBS treatments for epilepsy.
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