Pathological Networks Involving Dysmorphic Neurons in Type II Focal Cortical Dysplasia.
10.1007/s12264-022-00828-7
- Author:
Yijie SHAO
1
;
Qianqian GE
1
;
Jiachao YANG
1
;
Mi WANG
1
;
Yu ZHOU
1
;
Jin-Xin GUO
2
;
Mengyue ZHU
1
;
Jiachen SHI
1
;
Yiqi HU
1
;
Li SHEN
2
;
Zhong CHEN
3
;
Xiao-Ming LI
4
;
Jun-Ming ZHU
5
;
Jianmin ZHANG
6
;
Shumin DUAN
7
;
Jiadong CHEN
8
Author Information
1. Center for Neuroscience and Department of Neurosurgery of the Second Affiliated Hospital, NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, 310058, China.
2. The MOE Key Laboratory of Biosystems Homeostasis & Protection and Zhejiang Provincial Key Laboratory for Cancer Molecular Cell Biology, Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China.
3. Institute of Pharmacology & Toxicology, NHC and CAMS Key Laboratory of Medical Neurobiology, College of Pharmaceutical Sciences, School of Basic Medical Sciences, Zhejiang University, Hangzhou, 310058, China.
4. Center for Neuroscience and Department of Neurology of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, China.
5. Department of Neurosurgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.
6. Department of Neurosurgery of the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China. zjm135@zju.edu.cn.
7. Center for Neuroscience and Department of Neurosurgery of the Second Affiliated Hospital, NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, 310058, China. duanshumin@zju.edu.cn.
8. Center for Neuroscience and Department of Neurosurgery of the Second Affiliated Hospital, NHC and CAMS Key Laboratory of Medical Neurobiology, MOE Frontier Science Center for Brain Research and Brain-Machine Integration, School of Brain Science and Brain Medicine, Zhejiang University School of Medicine, Hangzhou, 310058, China. jardongchen@zju.edu.cn.
- Publication Type:Journal Article
- Keywords:
Dysmorphic neuron;
Excitation-inhibition balance;
Focal cortical dysplasia;
Morphological reconstruction;
Whole-cell patch-clamp recording
- MeSH:
Animals;
Drug Resistant Epilepsy/surgery*;
Epilepsy/pathology*;
Malformations of Cortical Development/pathology*;
Malformations of Cortical Development, Group I;
Mice;
Neurons/pathology*;
Seizures/pathology*
- From:
Neuroscience Bulletin
2022;38(9):1007-1024
- CountryChina
- Language:English
-
Abstract:
Focal cortical dysplasia (FCD) is one of the most common causes of drug-resistant epilepsy. Dysmorphic neurons are the major histopathological feature of type II FCD, but their role in seizure genesis in FCD is unclear. Here we performed whole-cell patch-clamp recording and morphological reconstruction of cortical principal neurons in postsurgical brain tissue from drug-resistant epilepsy patients. Quantitative analyses revealed distinct morphological and electrophysiological characteristics of the upper layer dysmorphic neurons in type II FCD, including an enlarged soma, aberrant dendritic arbors, increased current injection for rheobase action potential firing, and reduced action potential firing frequency. Intriguingly, the upper layer dysmorphic neurons received decreased glutamatergic and increased GABAergic synaptic inputs that were coupled with upregulation of the Na+-K+-Cl- cotransporter. In addition, we found a depolarizing shift of the GABA reversal potential in the CamKII-cre::PTENflox/flox mouse model of drug-resistant epilepsy, suggesting that enhanced GABAergic inputs might depolarize dysmorphic neurons. Thus, imbalance of synaptic excitation and inhibition of dysmorphic neurons may contribute to seizure genesis in type II FCD.
