JNeurosci The Journal of Neuroscience

Optogenetic Low-Frequency Stimulation of Specific Neuronal Populations Abates Ictogenesis

Zahra Shiri, Maxime Levesque, Guillaume Etter, Frederic Manseau, Sylvain Williams, and Massimo Avoli Contributed by Sloka S. Iyengar, PhD.

Contributed by Sloka Iyengar

Journal of Neuroscience 15 March 2017 37 (11) 2999-3008; DOI: https://doi.org/10.1523/JNEUROSCI.2244-16.2017

Objective – Seizures are caused by abnormal electrical activity in the brain. The brain includes of excitatory and inhibitory neurons (with a multitude of cell types under this broad classification). Excitatory and inhibitory neurons work in concert, and seizures are thought to arise when this balance goes awry. Anti-epileptic medications limit seizures in approximately two-thirds of the patient population, but the rest may have to resort to aggressive procedures like surgery (these patients are said to have “refractory” epilepsy). Low-frequency stimulation (LFS) is a procedure that could potentially be used for refractory epilepsy, because it has been shown to modify the behavior of neurons. However, one drawback of LFS is its non-specificity i.e. not being able to turn on and off specific cell types. Optogenetics is an experimental technique where certain neuronal populations can be turned on and off at will because the specific proteins they contain react to light of different wavelengths.

In the current study, the authors investigated effects of LFS with optogenetics in a part of the brain called the entorhinal cortex (EC). The EC was chosen because of its potential role in seizure generation. LFS with optogenetics was used to control the excitability of specific neuronal populations over time. All experiments were done in mice – after anesthesia, mice brain slices were made, and a drug called 4-AP was used to simulate seizures.

Results – The authors first confirmed that their technique of using optogenetics in mice could successfully target specific neuronal populations - Â they targeted one type of principal cell (excitatory neuron), and two types of interneurons (inhibitory neurons). The authors then found that LFS with optogenetics targeted to all three cell types reduced the rate of experimental seizures. The effect lasted for a longer time when principal cells were specifically targeted.

Interpretation – In this study of “in vitro” seizures (seizures produced outside the body; in this case, 4-AP was used in slices from a mouse brain), the authors found that LFS along with optogenetics reduced seizures. The authors checked just one model of seizure, and one question is whether LFS and optogenetics would reduce seizures caused by other techniques as well. Whether, and how this technique may help people with refractory seizures will require extensive experimentation.

Summary for specialists