Operative GABAergic inhibition in hippocampal CA1 pyramidal neurons in experimental epilepsy.
Patch-clamp recordings of CA1 interneurons and pyramidal cells were performed in hippocampal slices from kainate- or pilocarpine-treated rat models of temporal lobe epilepsy. We report that gamma-aminobutyric acid (GABA)ergic inhibition in pyramidal neurons is still functional in temporal lobe epilepsy because: (i) the frequency of spontaneous GABAergic currents is similar to that of control and (ii) focal electrical stimulation of interneurons evokes a hyperpolarization that prevents the generation of action potentials. In paired recordings of interneurons and pyramidal cells, synchronous interictal activities were recorded. Furthermore, large network-driven GABAergic inhibitory postsynaptic currents were present in pyramidal cells during interictal discharges. The duration of these interictal discharges was increased by the GABA type A antagonist bicuculline. We conclude that GABAergic inhibition is still present and functional in these experimental models and that the principal defect of inhibition does not lie in a complete disconnection of GABAergic interneurons from their glutamatergic inputs.
Esclapez
M
M
Institut National de la Santé et de la Recherche Médicale Unité 29, 123 Boulevard de Port-Royal, 75014 Paris, France.
Hirsch
J C
JC
Khazipov
R
R
Ben-Ari
Y
Y
Bernard
C
C
D000200:Action Potentials; D000818:Animals; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced; D058787:GABA-A Receptor Antagonists; D066298:In Vitro Techniques; D007395:Interneurons / Q000166:cytology / Q000502:physiology*; D008297:Male; D009433:Neural Inhibition / Q000502:physiology*; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D018079:Receptors, GABA / Q000378:metabolism*; D012640:Seizures
D058787:GABA-A Receptor Antagonists; D018079:Receptors, GABA