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Effects of a reduced efficacy of the KCC2 co-transporter in temporal lobe epilepsy: single neuron and network study
BMC Neurosciencevolume 16, Article number: P5 (2015)
Epilepsy is one of the most common neurological disorders. Seizures in about 40% of patients with temporal lobe epilepsies are pharmaco-resistant . In surgically removed hippocampal tissue from these patients, the KCC2 cotransporter is absent or non-functional in about 20 % of subicular pyramidal cells . KCC2 normally assures the maintenance of low intra-neuronal chloride levels  and also regulates potassium levels . Chloride concentration changes in the remaining pyramidal cells due to intensive GABAergic input during seizures could reverse the effects of GABA currents from inhibitory to excitatory [5, 6]. Such changes may shift a pyramidal cell into a periodic bursting regime associated with ictal discharges. Using a detailed biophysical model of a single cell incorporating these mechanisms of ionic homeostasis and a neural network model, we show that decreasing the activity of KCC2 pump leads to repetitive seizure-like firing in the pathologic network due to increased extracellular potassium and intracellular chloride (Fig. 1). This model provides insights into how a dysregulation of pyramidal cell chloride homeostasis due to reduced levels of the KCC2 cotransporter may lead to seizures in the epileptic human subiculum.
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This work has been supported by the following grants: ANR-10-LABX-0087 IEC, ANR-10-IDEX-0001-02 PSL, ERC-322721, FRM FDT20140930942. Especially we would like to thank Giri Krishnan for useful discussions.