title: Rebound burst firing in the reticular thalamus is not essential for pharmacological absence seizures in mice.
abstract: Intrinsic burst and rhythmic burst discharges (RBDs) are elicited by activation of T-type Ca(2+) 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 Ca(2+) 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.
authors: Center for Cognition and Sociality, Institute for Basic Science, Daejeon 305-811, Korea;Center for Functional Connectomics, Brain Science Institute, Korea Institute of Science and Technology, Seoul 136-791, Korea;Laboratory of Cell Death and Human Diseases, Department of Life Sciences, School of Life Sciences, Korea University, Seoul 136-701, Korea;
authors: Seung Eun
authors: SE
authors: Lee
authors: Center for Functional Connectomics, Brain Science Institute, Korea Institute of Science and Technology, Seoul 136-791, Korea;
authors: Jaekwang
authors: J
authors: Lee
authors: Center for Cognition and Sociality, Institute for Basic Science, Daejeon 305-811, Korea;
authors: Charles
authors: C
authors: Latchoumane
authors: Center for Cognition and Sociality, Institute for Basic Science, Daejeon 305-811, Korea;
authors: Boyoung
authors: B
authors: Lee
authors: Center for Neural Science, Brain Science Institute, Korea Institute of Science and Technology, Seoul 136-791, Korea;
authors: Soo-Jin
authors: SJ
authors: Oh
authors: Center for Neural Science, Brain Science Institute, Korea Institute of Science and Technology, Seoul 136-791, Korea;
authors: Zahangir Alam
authors: ZA
authors: Saud
authors: Center for Neural Science, Brain Science Institute, Korea Institute of Science and Technology, Seoul 136-791, Korea;
authors: Cheongdahm
authors: C
authors: Park
authors: Department of Protein Sciences, Amgen, Inc., Thousand Oaks, CA 91320;
authors: Ning
authors: N
authors: Sun
authors: Department of Biotechnology, College of Life Science and Biotechnology, Translational Research Center for Protein Function Control, Yonsei University, Seoul 120-749, Korea; and.
authors: Eunji
authors: E
authors: Cheong
authors: Institute of Biomedical Sciences, Academia Sinica, Nankang, Taipei 115, Taiwan.
authors: Chien-Chang
authors: CC
authors: Chen
authors: Laboratory of Cell Death and Human Diseases, Department of Life Sciences, School of Life Sciences, Korea University, Seoul 136-701, Korea;
authors: Eui-Ju
authors: EJ
authors: Choi
authors: Center for Functional Connectomics, Brain Science Institute, Korea Institute of Science and Technology, Seoul 136-791, Korea;Center for Neural Science, Brain Science Institute, Korea Institute of Science and Technology, Seoul 136-791, Korea;
authors: C Justin
authors: CJ
authors: Lee
authors: Center for Cognition and Sociality, Institute for Basic Science, Daejeon 305-811, Korea; shin@ibs.re.kr.
authors: Hee-Sup
authors: HS
authors: Shin
mesh_terms: D015107:4-Butyrolactone / Q000633:toxicity; D000200:Action Potentials; D000818:Animals; D020747:Calcium Channels, T-Type / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D055724:Electrophysiological Phenomena; D004832:Epilepsy, Absence / Q000139:chemically induced / Q000503:physiopathology*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D018408:Patch-Clamp Techniques; D013787:Thalamic Nuclei / Q000503:physiopathology*
chemical_list: C504883:Cacna1h protein, mouse; C534770:Cacna1i protein, mouse; D020747:Calcium Channels, T-Type; D015107:4-Butyrolactone