Pathological Networks Involving Dysmorphic Neurons in Type ⅡFocal Cortical Dysplasia  

作　　者：Yijie Shao Qianqian Ge Jiachao Yang Mi Wang Yu Zhou Jin-Xin Guo Mengyue Zhu Jiachen Shi Yiqi Hu Li Shen Zhong Chen Xiao-Ming Li Jun-Ming Zhu Jianmin Zhang Shumin Duan Jiadong Chen 

机构地区：[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]Department of Neurosurgery of the Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,310009,China [3]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 [4]Department of Orthopedic Surgery,School of Medicine,the Second Affiliated Hospital,Zhejiang University,Hangzhou,310009,China [5]Hangzhou Innovation Center,Zhejiang University,Hangzhou,310058,China [6]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 [7]Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province,College of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou,310058,China [8]Center for Neuroscience and Department of Neurology of the Second Affiliated Hospital,Zhejiang University School of Medicine,Hangzhou,310058,China [9]NHC and CAMS Key Laboratory of Medical Neurobiology,Center for Brain Science and Brain-Inspired Intelligence,Joint Institute for Genetics and Genome Medicine between,Guangdong Hong Kong Macao Greater Bay Area,Zhejiang University and the University of Toronto,Zhejiang University School of Medicine,Hangzhou,310058,China

出　　处：《Neuroscience Bulletin》2022年第9期1007-1024,共18页神经科学通报（英文版）

基　　金：supported by grants from the Ministry of Science and Technology(2019YFA0110103);the National Natural Science Foundation of China(81870898,82071287,and 81870916);the Fundamental Research Funds for the Central Universities(2019FZA7009 and 2021FZZX001-37);the Zhejiang Provincial Natural Science Foundation(LR18H090002).

摘　　要：Focal cortical dysplasia(FCD)is one of the most common causes of drug-resistant epilepsy.Dysmorphic neurons are the major histopathological feature of typeⅡFCD,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 typeⅡFCD,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 typeⅡFCD.

关 键 词：Focal cortical dysplasia Dysmorphic neuron Whole-cell patch-clamp recording Morphological reconstruction Excitation-inhibition balance 

分 类 号：R338[医药卫生—人体生理学]