[Epileptiform activities generated in vitro by human temporal lobe tissue].
Drug-resistant partial epilepsies, including temporal lobe epilepsies with hippocampal sclerosis and cortical dysplasias, offer the opportunity to study human epileptic activity in vitro since the preferred therapy often consists of the surgical removal of the epileptogenic zone. Slices of this tissue retain functional neuronal networks and may generate epileptic activity. The properties of cells in this tissue do not seem to be significantly changed, but excitatory synaptic characteristics are enhanced and GABAergic inhibition is preserved. Typically, epileptic activity is not generated spontaneously by the neocortex, whether dysplastic or not, but can be induced by convulsants. The initiation of ictal discharges in neocortex depends on both GABAergic signaling and increased extracellular potassium. In contrast, a spontaneous interictal-like activity is generated by tissues from patients with temporal lobe epilepsies associated with hippocampal sclerosis. This activity is initiated not in the hippocampus but in the subiculum, an output region that projects to the entorhinal cortex. Interictal events seem to be triggered by GABAergic cells, which paradoxically excite approximately 20% of subicular pyramidal cells, while simultaneously inhibiting the majority. Interictal discharges are therefore sustained by both GABAergic and glutamatergic signaling. The atypical depolarizing effects of GABA depend on a pathological elevation in the basal levels of chloride in some subicular cells, similar to those of developmentally immature cells. This defect is caused by the perturbation of the expression of the cotransporters regulating the intracellular chloride concentration, the importer NKCC1, and the extruder KCC2. Blockade of excessive NKCC1 by the diuretic bumetanide restores intracellular chloride and thus hyperpolarizing GABAergic actions, suppressing interictal activity.
Huberfeld
G
G
Inserm U739 Cortex & Epilepsie, université Pierre-et-Marie-Curie, CHU de la Pitié-Salpêtrière, 105, boulevard de l'Hôpital, 75013 Paris, France. gilles.huberfeld@chups.jussieu.fr
Clemenceau
S
S
Cohen
I
I
Pallud
J
J
Wittner
L
L
Navarro
V
V
Baulac
M
M
Miles
R
R
D000328:Adult; D004594:Electrophysiology; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology*; D006624:Hippocampus / Q000503:physiopathology; D006801:Humans; D066298:In Vitro Techniques; D009474:Neurons / Q000502:physiology; D013702:Temporal Lobe / Q000503:physiopathology*