Rebound burst firing in the reticular thalamus is not essential for pharmacological absence seizures in mice

Seung Eun Lee, Jaekwang Lee, Charles Latchoumane, Boyoung Lee, Soo Jin Oh, Zahangir Alam Saud, Cheongdahm Park, Ning Sun, Eunji Cheong, Chien Chang Chen, Eui Ju Choi, Changjoon Lee, Hee Sup Shin

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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 spikeand- 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 druginduced 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.

Original languageEnglish
Pages (from-to)11828-11833
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number32
DOIs
Publication statusPublished - 2014 Aug 12

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Absence Epilepsy
Thalamic Nuclei
Thalamus
Pharmacology
Neurons
Pharmaceutical Preparations
Genes
Maintenance

ASJC Scopus subject areas

  • General

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Rebound burst firing in the reticular thalamus is not essential for pharmacological absence seizures in mice. / Lee, Seung Eun; Lee, Jaekwang; Latchoumane, Charles; Lee, Boyoung; Oh, Soo Jin; Saud, Zahangir Alam; Park, Cheongdahm; Sun, Ning; Cheong, Eunji; Chen, Chien Chang; Choi, Eui Ju; Lee, Changjoon; Shin, Hee Sup.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 111, No. 32, 12.08.2014, p. 11828-11833.

Research output: Contribution to journalArticle

Lee, SE, Lee, J, Latchoumane, C, Lee, B, Oh, SJ, Saud, ZA, Park, C, Sun, N, Cheong, E, Chen, CC, Choi, EJ, Lee, C & Shin, HS 2014, 'Rebound burst firing in the reticular thalamus is not essential for pharmacological absence seizures in mice', Proceedings of the National Academy of Sciences of the United States of America, vol. 111, no. 32, pp. 11828-11833. https://doi.org/10.1073/pnas.1408609111
Lee, Seung Eun ; Lee, Jaekwang ; Latchoumane, Charles ; Lee, Boyoung ; Oh, Soo Jin ; Saud, Zahangir Alam ; Park, Cheongdahm ; Sun, Ning ; Cheong, Eunji ; Chen, Chien Chang ; Choi, Eui Ju ; Lee, Changjoon ; Shin, Hee Sup. / Rebound burst firing in the reticular thalamus is not essential for pharmacological absence seizures in mice. In: Proceedings of the National Academy of Sciences of the United States of America. 2014 ; Vol. 111, No. 32. pp. 11828-11833.
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AU - Lee, Boyoung

AU - Oh, Soo Jin

AU - Saud, Zahangir Alam

AU - Park, Cheongdahm

AU - Sun, Ning

AU - Cheong, Eunji

AU - Chen, Chien Chang

AU - Choi, Eui Ju

AU - Lee, Changjoon

AU - Shin, Hee Sup

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