Chang Bomi 변준원 Kim Ko Keun 이성은 이보영 김기선 류훈 신희섭 정은지 2024-01-19T12:03:53Z 2024-01-19T12:03:53Z 2022-06-30 2022-04 1226-2560 https://pubs.kist.re.kr/handle/201004/115277 Absence seizures are caused by abnormal synchronized oscillations in the thalamocortical (TC) circuit, which result in widespread spike-and-wave discharges (SWDs) on electroencephalography (EEG) as well as impairment of consciousness. Thalamic reticular nucleus (TRN) and TC neurons are known to interact dynamically to generate TC circuitry oscillations during SWDs. Clinical studies have suggested the association of Plcβ1 with early-onset epilepsy, including absence seizures. However, the brain regions and circuit mechanisms related to the generation of absence seizures with Plcβ1 deficiency are unknown. In this study, we found that loss of Plcβ1 in mice caused spontaneous complex-type seizures, including convulsive and absence seizures. Importantly, TRN-specific deletion of Plcβ1 led to the development of only spontaneous SWDs, and no other types of seizures were observed. Ex vivo slice patch recording demonstrated that the number of spikes, an intrinsic TRN neuronal property, was significantly reduced in both tonic and burst firing modes in the absence of Plcβ1 . We conclude that the loss of Plcβ1 in the TRN leads to decreased excitability and impairs normal inhibitory neuronal function, thereby disrupting feedforward inhibition of the TC circuitry, which is sufficient to cause hypersynchrony of the TC system and eventually leads to spontaneous absence seizures. Our study not only provides a novel mechanism for the induction of SWDs in Plcβ1 -deficient patients but also offers guidance for the development of diagnostic and therapeutic tools for absence epilepsy. English 한국뇌신경과학회 Deletion of Phospholipase C β1 in the Thalamic Reticular Nucleus Induces Absence Seizures Article 10.5607/en22007 1 Experimental Neurobiology, v.31, no.2, pp.116 - 130 Experimental Neurobiology 31 2 116 130 Y scie scopus kci ART002846379 000911405600005 Medicine, Research & Experimental Neurosciences Research & Experimental Medicine Neurosciences & Neurology Article CA2+ CHANNELS CALCIUM CURRENTS EPILEPSY CONNECTIVITY OSCILLATIONS SYNCHRONY ATTENTION NEURONS ROLES Thalamocortical neuronal system Absence seizure Spike and wave discharges Thalamic reticular nucleus Plcβ1