丘脑网状核中磷脂酶C β1缺失诱导癫痫发作

IF 1.8 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Experimental Neurobiology Pub Date : 2022-04-30 DOI:10.5607/en22007
Bomi Chang, Junweon Byun, Ko Keun Kim, Seung Eun Lee, Boyoung Lee, Key‐Sun Kim, Hoon Ryu, Hee-Sup Shin, Eunji Cheong
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引用次数: 0

摘要

失神性癫痫发作是由丘脑皮质(TC)回路中的异常同步振荡引起的,这会导致脑电图(EEG)上广泛的棘波放电(SWD)以及意识障碍。丘脑网状核(TRN)和TC神经元在SWD过程中动态相互作用,产生TC电路振荡。临床研究表明Plcβ1与早发性癫痫(包括失神性癫痫)有关。然而,与Plcβ1缺乏症引起缺席性癫痫发作有关的大脑区域和回路机制尚不清楚。在这项研究中,我们发现小鼠Plcβ1的缺失会导致自发的复杂型癫痫发作,包括抽搐和缺席癫痫发作。重要的是,TRN特异性Plcβ1缺失仅导致自发性SWD的发展,未观察到其他类型的癫痫发作。离体切片补片记录表明,在缺乏Plcβ1的情况下,作为TRN神经元固有特性的尖峰数量在紧张和突发放电模式下都显著减少。我们的结论是,TRN中Plcβ1的缺失导致兴奋性降低,并损害正常的抑制性神经元功能,从而破坏TC电路的前馈抑制,这足以导致TC系统的超同步,并最终导致自发缺席癫痫发作。我们的研究不仅为Plcβ1缺陷患者诱发SWD提供了一种新的机制,而且为开发缺席癫痫的诊断和治疗工具提供了指导。
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Deletion of Phospholipase C β1 in the Thalamic Reticular Nucleus Induces Absence Seizures
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.
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来源期刊
Experimental Neurobiology
Experimental Neurobiology Neuroscience-Cellular and Molecular Neuroscience
CiteScore
4.30
自引率
4.20%
发文量
29
期刊介绍: Experimental Neurobiology is an international forum for interdisciplinary investigations of the nervous system. The journal aims to publish papers that present novel observations in all fields of neuroscience, encompassing cellular & molecular neuroscience, development/differentiation/plasticity, neurobiology of disease, systems/cognitive/behavioral neuroscience, drug development & industrial application, brain-machine interface, methodologies/tools, and clinical neuroscience. It should be of interest to a broad scientific audience working on the biochemical, molecular biological, cell biological, pharmacological, physiological, psychophysical, clinical, anatomical, cognitive, and biotechnological aspects of neuroscience. The journal publishes both original research articles and review articles. Experimental Neurobiology is an open access, peer-reviewed online journal. The journal is published jointly by The Korean Society for Brain and Neural Sciences & The Korean Society for Neurodegenerative Disease.
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