KMID : 0892920220310020116
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Experimental Neurobiology 2022 Volume.31 No. 2 p.116 ~ p.130
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Deletion of Phospholipase C ¥â1 in the Thalamic Reticular Nucleus Induces Absence Seizures
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Chang Bomi
Byun Jun-Weon Kim Ko-Keun Lee Seung-Eun Lee Bo-Young Kim Key-Sun Ryu Hoon Shin Hee-Sup Cheong Eun-Ji
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Abstract
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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 Plc¥â1 with early-onset epilepsy, including absence seizures. However, the brain regions and circuit mechanisms related to the generation of absence seizures with Plc¥â1 deficiency are unknown. In this study, we found that loss of Plc¥â1 in mice caused spontaneous complex-type seizures, including convulsive and absence seizures. Importantly, TRN-specific deletion of Plc¥â1 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 Plc¥â1 . We conclude that the loss of Plc¥â1 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 Plc¥â1 -deficient patients but also offers guidance for the development of diagnostic and therapeutic tools for absence epilepsy.
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KEYWORD
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Thalamocortical neuronal system, Absence seizure, Spike and wave discharges, Thalamic reticular nucleus, Plc¥â1
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