Authors :
Presenting Author: Jiaoyang Wang, PhD – Guangzhou Laboratory
Yue Gui, Scientist – Guangzhou Laboratory; Huanling Lai, Associate professor – Guangzhou Laboratory; Xiaonan Li, Assistant professor – Guangzhou Laboratory; Yue Xing, Scientist – Guangzhou Laboratory; XIAOFENG YANG, Professor – Guangzhou Laboratory
Rationale:
Neural modulation based on epilepsy network has been applied to epilepsy treatment, and the targets of modulation are usually key nodes in the epilepsy network, with the centromedian thalamic nucleus (CMT) being an important one. However, the network concections of CMT in the epileptic circuit is not yet clear. This study aims to explore the connectivity of CMT in the temporal lobe epilepsy (TLE) circuit.
Methods:
Hippocampal seizures were induced by four aminopyridine in rats. The rats were randomly divided into three groups. The first group used a 3D tetrode array to observe the propagation of seizures. In the second group, we chemically damaged the CMT to investigate its role in the hippocampal epileptic network. In the third group, we used chemogenetic techniques to selectively inhibit excitatory neurons in CMT and observed changes in the epileptogenic network during hippocampal seizures. Klustakwik and self-written scripts are used for off-line singleton sorting and clustering.
Results:
The putative excitatory neurons in hippocampus and inhibitory neurons in CMT showed significant increase during seizures, it indicated an “excitatory-to-inhibitory” connectivity from hippocampus to CMT for seizure spread. After CMT damage, contralateral hippocampal seizures are terminated and ipsilateral seizure was relieved. Specific suppression of CMT excitatory neurons decreased the activity of hippocampal inhibitory neurons, these two groups indicated “inhibitory-to-excitatory” and “excitatory-to-inhibitory” connectivity from CMT to hippocampus for seizure modulation.
Conclusions:
The ‘inhibitory-excitatory’ and ‘excitatory-inhibitory’ neural network between CMT and hippocampus were correlated to hippocampal seizure spread and modulation. CMT would be a more specific neural modulation target in clinical application.
Funding:
This work was funded by the National Natural Science Foundation of China (XFY 82271492
，81971202, 81671367, and 81790653)