Slaght Seán J, Paz Tamar, Chavez Mario, Deniau Jean-Michel, Mahon Séverine, Charpier Stéphane
Institut National de la Santé et de la Recherche Médicale U114, Chaire de Neuropharmacologie, Collège de France, 75231 Paris Cedex 05, France.
J Neurosci. 2004 Jul 28;24(30):6816-25. doi: 10.1523/JNEUROSCI.1449-04.2004.
Absence seizures are characterized by impairment of consciousness associated with widespread bilaterally synchronous spike-and-wave discharges (SWDs) in the electroencephalogram (EEG), which reflect highly synchronized oscillations in thalamocortical networks. Although recent pharmacological studies suggest that the basal ganglia could provide a remote control system for absence seizures, the mechanisms of propagation of epileptic discharges in these subcortical nuclei remain unknown. In the present study, we provide the first description of the electrical events in the corticostriatal pathway during spontaneous SWDs in the genetic absence epilepsy rats from Strasbourg (GAERS), a genetic model of absence epilepsy. In corticostriatal neurons, the SWDs were associated with suprathreshold rhythmic depolarizations in-phase with local EEG spikes. Consistent with this synchronized firing in their excitatory cortical afferents, striatal output neurons (SONs) exhibited, during SWDs, large-amplitude rhythmic synaptic depolarizations. However, SONs did not discharge during SWDs. Instead, the rhythmic synaptic excitation of SONs was shunted by a Cl(-)-dependent increase in membrane conductance that was temporally correlated with bursts of action potentials in striatal GABAergic interneurons. The reduced SON excitability accompanying absence seizures may participate in the control of SWDs by affecting the flow of cortical information within the basal ganglia circuits.
失神发作的特征是意识障碍,脑电图(EEG)显示双侧广泛同步的棘慢波放电(SWD),这反映了丘脑皮质网络中的高度同步振荡。尽管最近的药理学研究表明基底神经节可能为失神发作提供一个远程控制系统,但癫痫放电在这些皮质下核团中的传播机制仍不清楚。在本研究中,我们首次描述了来自斯特拉斯堡的遗传性失神癫痫大鼠(GAERS),一种失神癫痫的遗传模型,在自发性SWD期间皮质纹状体通路中的电活动。在皮质纹状体神经元中,SWD与与局部EEG尖峰同相的阈上节律性去极化相关。与其兴奋性皮质传入纤维中的这种同步放电一致,纹状体输出神经元(SON)在SWD期间表现出大幅度的节律性突触去极化。然而,SON在SWD期间并不放电。相反,SON的节律性突触兴奋被Cl(-)依赖性膜电导增加所分流,该增加与纹状体GABA能中间神经元的动作电位爆发在时间上相关。失神发作时SON兴奋性降低可能通过影响基底神经节回路内的皮质信息流参与SWD的控制。