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• W4360977237 endingPage "106102" @default.
• W4360977237 startingPage "106102" @default.
• W4360977237 abstract "Epilepsy is based on abnormal neuronal activities that have historically been suggested to arise from an excess of excitation and a defect of inhibition, or in other words from an excessive glutamatergic drive not balanced by GABAergic activity. More recent data however indicate that GABAergic signaling is not defective at focal seizure onset and may even be actively involved in seizure generation by providing excitatory inputs. Recordings of interneurons revealed that they are active at seizure initiation and that their selective and time-controlled activation using optogenetics triggers seizures in a more general context of increased excitability. Moreover, GABAergic signaling appears to be mandatory at seizure onset in many models. The main pro-ictogenic effect of GABAergic signaling is the depolarizing action of GABAA conductance which may occur when an excessive GABAergic activity causes Cl- accumulation in neurons. This process may combine with background dysregulation of Cl-, well described in epileptic tissues. Cl- equilibrium is maintained by (Na+)/K+/Cl- co-transporters, which can be defective and therefore favor the depolarizing effects of GABA. In addition, these co-transporters further contribute to this effect as they mediate K+ outflow together with Cl- extrusion, a process that is responsible for K+ accumulation in the extracellular space and subsequent increase of local excitability. The role of GABAergic signaling in focal seizure generation is obvious but its complex dynamics and balance between GABAA flux polarity and local excitability still remain to be established, especially in epileptic tissues where receptors and ion regulators are disrupted and in which GABAergic signaling rather plays a 2 faces Janus role." @default.
• W4360977237 created "2023-03-30" @default.
• W4360977237 creator A5000510243 @default.
• W4360977237 creator A5077630349 @default.
• W4360977237 date "2023-05-01" @default.
• W4360977237 modified "2023-10-15" @default.
• W4360977237 title "GABAergic circuits drive focal seizures" @default.
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