Deletion of phospholipase C β4 in thalamocortical relay nucleus leads to absence seizures

Eunji Cheong, Yihong Zheng, Kyoobin Lee, Jungryun Lee, Seongwook Kim, Maryam Sanati, Sukyung Lee, Yeon Soo Kim, Hee Sup Shin

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Absence seizures are characterized by cortical spike-wave discharges (SWDs) on electroencephalography, often accompanied by a shift in the firing pattern of thalamocortical (TC) neurons from tonic to burst firing driven by T-type Ca2+ currents. We recently demonstrated that the phospholipase C β4 (PLCβ4) pathway tunes the firing mode of TC neurons via the simultaneous regulation of T- and L-type Ca2+ currents, which prompted us to investigate the contribution of TC firing modes to absence seizures. PLCβ4-deficient TC neurons were readily shifted to the oscillatory burst firing mode after a slight hyperpolarization of membrane potential. TC-limited knockdown as well as whole-animal knockout of PLCβ4 induced spontaneous SWDs with simultaneous behavioral arrests and increased the susceptibility to drug-induced SWDs, indicating that the deletion of thalamic PLCβ4 leads to the genesis of absence seizures. The SWDs were effectively suppressed by thalamic infusion of a T-type, but not an L-type, Ca2+ channel blocker. These results reveal a primary role of TC neurons in the genesis of absence seizures and provide strong evidence that an alteration of the firing property of TC neurons is sufficient to generate absence seizures. Our study presents PLCβ4-deficient mice as a potential animal model for absence seizures.

Original languageEnglish
Pages (from-to)21912-21917
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number51
DOIs
Publication statusPublished - 2009 Dec 22

All Science Journal Classification (ASJC) codes

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