Kv1.1 channels inhibition in the rat motor cortex recapitulates seizures associated with anti-LGI1 encephalitis

被引：12

作者：

Baudin, Paul ^{[1
]}

Whitmarsh, Stephen ^{[1
]}

Cousyn, Louis ^{[1
,2
]}

Roussel, Delphine ^{[1
]}

Lecas, Sarah ^{[1
]}

Lehongre, Katia ^{[1
]}

Charpier, Stephane ^{[1
]}

Mahon, Severine ^{[1
]}

Navarro, Vincent ^{[1
,2
,3
]}

机构：

[1] Sorbonne Univ, Pitie Salpetriere Hosp, AP HP, Paris Brain Inst,Inst Cerveau,ICM,INSERM,CNRS, Paris, France

[2] Hop La Pitie Salpetriere, AP HP, DMU Neurosci, Epilepsy Unit, Paris, France

[3] Hop La Pitie Salpetriere, AP HP, Ctr Reference Rare Epilepsies, Paris, France

来源：

PROGRESS IN NEUROBIOLOGY | 2022年 / 213卷

关键词：

LGI1; Kv1; 1; Tonic-dystonic seizures; Epilepsy; Autoimmune encephalitis; FACIOBRACHIAL DYSTONIC SEIZURES; K+ CHANNELS; BARREL CORTEX; INTRINSIC EXCITABILITY; CORTICAL-NEURONS; DENDROTOXIN-K; LGI1; ABSENCE; AUTOANTIBODIES; IMMUNOTHERAPY;

D O I：

10.1016/j.pneurobio.2022.102262

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Autoimmune encephalitis associated with antibodies directed against the leucine-rich glioma inactivated 1 (LGI1) protein is responsible for specific tonic-dystonic motor seizures. Although dysfunctions in neuronal excitability have been associated with anti-LGI1 autoantibodies, their relation to seizures remain inconclusive. We developed a new in vivo experimental rat model to determine whether inhibition of Kv1.1 channels by dentrotoxin-K (DTX) in the primary motor cortex (M1) could recapitulate the human seizures and to elucidate their subtending cortical mechanisms. Comparing electro-clinical features of DTX-induced seizures in rats with those recorded from a cohort of anti-LGI1 encephalitis patients revealed striking similarities in their electroencephalographic (EEG) signature, frequency of recurrence and semiology. By combining multi-site extracellular and intracellular recordings of M1 pyramidal neurons in DTX rats, we demonstrated that the blockade of Kv1.1 channels induced a sequence of changes in neuronal excitability and synaptic activity, leading to massive suprathreshold membrane depolarizations underlying the paroxysmal EEG activity. Our results suggest the central role of Kv1.1 channels disruption in the emergence of anti-LGI1-associated seizures and suggest that this new rodent model could serve future investigations on ictogenesis in autoimmune encephalitis.

引用

页数：15

共 72 条

[1] Cortical neurons and networks are dormant but fully responsive during isoelectric brain state [J].