A disinhibitory nigra-parafascicular pathway amplifies seizure in temporal lobe epilepsy
| Autor: | Wenkai Lin, Ping Dong, Shihong Zhang, Ting-Ting Hu, Junli Zhao, Shuming Duan, Yi Guo, Shuang Wang, Ying Wang, Weiwei Hu, Cenglin Xu, Zhong Chen, Lingyu Xu, Yi Wang, Heming Cheng, Yu-Dong Zhou, Bin Chen, Liying Chen |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male Patch-Clamp Techniques Science General Physics and Astronomy Mice Transgenic Biology Optogenetics Severity of Illness Index General Biochemistry Genetics and Molecular Biology Temporal lobe Stereotaxic Techniques 03 medical and health sciences Epilepsy Mice 0302 clinical medicine Neural Pathways Biological neural network medicine Animals Humans GABAergic Neurons lcsh:Science Multidisciplinary Kindling Intralaminar Thalamic Nuclei General Chemistry medicine.disease equipment and supplies Research Highlight Electrodes Implanted Substantia Nigra Disease Models Animal 030104 developmental biology Epilepsy Temporal Lobe nervous system Stereotaxic technique biology.protein GABAergic lcsh:Q Neuroscience 030217 neurology & neurosurgery Parvalbumin |
| Zdroj: | Nature Communications, Vol 11, Iss 1, Pp 1-16 (2020) Neurosci Bull |
| ISSN: | 2041-1723 |
| Popis: | The precise circuit of the substantia nigra pars reticulata (SNr) involved in temporal lobe epilepsy (TLE) is still unclear. Here we found that optogenetic or chemogenetic activation of SNr parvalbumin+ (PV) GABAergic neurons amplifies seizure activities in kindling- and kainic acid-induced TLE models, whereas selective inhibition of these neurons alleviates seizure activities. The severity of seizures is bidirectionally regulated by optogenetic manipulation of SNr PV fibers projecting to the parafascicular nucleus (PF). Electrophysiology combined with rabies virus-assisted circuit mapping shows that SNr PV neurons directly project to and functionally inhibit posterior PF GABAergic neurons. Activity of these neurons also regulates seizure activity. Collectively, our results reveal that a long-range SNr-PF disinhibitory circuit participates in regulating seizure in TLE and inactivation of this circuit can alleviate severity of epileptic seizures. These findings provide a better understanding of pathological changes from a circuit perspective and suggest a possibility to precisely control epilepsy. The neural circuits through which the substantia nigra pars reticulata (SNr) exerts its role in epilepsy control are not known. Here the authors reveal that a long-range SNr-parafascicular nucleus disinhibitory circuit participates in regulating seizures in temporal lobe epilepsy and inhibition of this circuit can alleviate severity of epileptic seizures. |
| Databáze: | OpenAIRE |
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