Yi Wang, Cenglin Xu, Zhenghao Xu, Caihong Ji, Jiao Liang, Ying Wang, Bin Chen, Xiaohua Wu, Feng Gao, Shuang Wang, Yi Guo, Xiaoming Li, Jianhong Luo, Shumin Duan and Zhong Chen*.Depolarized GABAergic signaling in subicular microcircuits mediates generalized seizure in temporal lobe epilepsy. Neuron, 2017 July 4.
Secondary generalized seizure (sGS) is a major source of disability in temporal lobe epilepsy (TLE) with unclear cellular/circuit mechanisms. Here we found that clinical TLE patients with sGS showed reduced volume specifically in the subiculum compared with those without sGS. Further, using optogenetics and extracellular electrophysiological recording in mouse models, we found that photoactivation of subicular GABAergic neurons retarded sGS acquisition by inhibiting the firing of pyramidal neurons. Once sGS had been stably acquired, photoactivation of GABAergic neurons aggravated sGS expression via depolarized GABAergic signaling. Subicular parvalbu- min, but not somatostatin subtype GABAergic, neu- rons were easily depolarized in sGS expression. Finally, photostimulation of subicular pyramidal neu- rons genetically targeted with proton pump Arch, rather than chloride pump NpHR3.0, alleviated sGS expression. These results demonstrated that depolar- ized GABAergic signaling in subicular microcircuit mediates sGS in TLE. This may be of therapeutic interest in understanding the pathological neuronal circuitry underlying sGS.
Vedio Abstract (will be published on July 5th): https://youtu.be/OqVMGJc_TKE