Cheong, Eunji Zheng, Yihong Lee, Kyoobin Lee, Jungryun Kim, Seongwook Sanati, Maryam Lee, Sukyung Kim, Yeon-Soo Shin, Hee-Sup 2024-01-20T20:03:44Z 2024-01-20T20:03:44Z 2021-09-05 2009-12-22 0027-8424 https://pubs.kist.re.kr/handle/201004/131863 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 beta 4 (PLC beta 4) 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. PLC beta 4-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 PLC beta 4 induced spontaneous SWDs with simultaneous behavioral arrests and increased the susceptibility to drug-induced SWDs, indicating that the deletion of thalamic PLC beta 4 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 PLC beta 4-deficient mice as a potential animal model for absence seizures. English NATL ACAD SCIENCES VOLTAGE-ACTIVATED CURRENTS GAMMA-HYDROXYBUTYRIC ACID WAVE DISCHARGES SPONTANEOUS SPIKE THALAMIC NEURONS CALCIUM-CHANNEL CA2+ CHANNELS MOUSE MODELS EPILEPSY MECHANISMS Deletion of phospholipase C beta 4 in thalamocortical relay nucleus leads to absence seizures Article 10.1073/pnas.0912204106 1 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.106, no.51, pp.21912 - 21917 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 106 51 21912 21917 scie scopus 000272994200081 2-s2.0-76049101652 Multidisciplinary Sciences Science & Technology - Other Topics Article VOLTAGE-ACTIVATED CURRENTS GAMMA-HYDROXYBUTYRIC ACID WAVE DISCHARGES SPONTANEOUS SPIKE THALAMIC NEURONS CALCIUM-CHANNEL CA2+ CHANNELS MOUSE MODELS EPILEPSY MECHANISMS epilepsy gene knockdown knockout mice thalamus