한빛사논문
- 조회1,872
Abstract
Seung Eun Leea,b,c, Jaekwang Leeb, Charles Latchoumanea, Boyoung Leea, Soo-Jin Ohd, Zahangir Alam Saudd,1, Cheongdahm Parkd, Ning Sune, Eunji Cheongf, Chien-Chang Cheng, Eui-Ju Choic, C. Justin Leeb,d, and Hee-Sup Shina,2
aCenter for Cognition and Sociality, Institute for Basic Science, Daejeon 305-811, Korea; bCenter for Functional Connectomics, Brain Science Institute, Korea Institute of Science and Technology, Seoul 136-791, Korea; cLaboratory of Cell Death and Human Diseases, Department of Life Sciences, School of Life Sciences, Korea University, Seoul 136-701, Korea; dCenter for Neural Science, Brain Science Institute, Korea Institute of Science and Technology, Seoul 136-791, Korea; eDepartment of Protein Sciences, Amgen, Inc., Thousand Oaks, CA 91320; fDepartment of Biotechnology, College of Life Science and Biotechnology, Translational Research Center for Protein Function Control, Yonsei University, Seoul 120-749, Korea; and gInstitute of Biomedical Sciences, Academia Sinica, Nankang, Taipei 115, Taiwan
Abstract
Intrinsic burst and rhythmic burst discharges (RBDs) are elicited by activation of T-type Ca2+ channels in the thalamic reticular nucleus (TRN). TRN bursts are believed to be critical for generation and maintenance of thalamocortical oscillations, leading to the spike-and-wave discharges (SWDs), which are the hallmarks of absence seizures. We observed that the RBDs were completely abolished, whereas tonic firing was significantly increased, in TRN neurons from mice in which the gene for the T-type Ca2+ channel, CaV3.3, was deleted (CaV3.3-/-). Contrary to expectations, there was an increased susceptibility to drug-induced SWDs both in CaV3.3-/- mice and in mice in which the CaV3.3 gene was silenced predominantly in the TRN. CaV3.3-/- mice also showed enhanced inhibitory synaptic drive onto TC neurons. Finally, a double knockout of both CaV3.3 and CaV3.2, which showed complete elimination of burst firing and RBDs in TRN neurons, also displayed enhanced drug-induced SWDs and absence seizures. On the other hand, tonic firing in the TRN was increased in these mice, suggesting that increased tonic firing in the TRN may be sufficient for drug-induced SWD generation in the absence of burst firing. These results call into question the role of burst firing in TRN neurons in the genesis of SWDs, calling for a rethinking of the mechanism for absence seizure induction.
1Present address: Department of Biochemistry and Molecular Biology, University of Rajshahi, Rajshahi-6205, Bangladesh.
2To whom correspondence should be addressed.
Author contributions: S.E.L., E.C., C.J.L., and H.-S.S. designed the experiments; S.E.L., J.L., B.L., S.-J.O., Z.A.S., and C.P. performed research; S.E.L. and C.L. analyzed the data; N.S. designed and made the construct for homologous recombination; E.-J.C. discussed the results and commented on the manuscript; and C.-C.C. generated CaV3.2 mouse line; and S.E.L., E.C., C.J.L., and H.-S.S. wrote the paper.
논문정보
- Research article
- 2014년 07월 (BRIC 등록일 2014-08-01)
- 국내(교신)+국외 연구진
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