Opposite Changes in GABA_A Receptor Function in the CA1‐3 Area and Fascia Dentata of Kindled Rat Hippocampus

Abstract

Muscimol‐stimulated radiotracer 36Cl− uptake in synaptoneurosomes was used to investigate the function of the GABAA receptor complex in the CA1‐3 area and fascia dentata (granular and molecular layers and hilus) of rats kindled by stimulation, twice a day, of the Schaffer collateral fibers. Two kindled groups were studied: (a) 24 h after the last generalized tonic‐clonic seizure [fully kindled (FK) stage] and (b) 28 days after the last generalized seizure (long‐term stage). Synaptoneurosomes were prepared in parallel from subslices of the CA1‐3 area and fascia dentata. In FK animals, the muscimol‐stimulated 36Cl− uptake was significantly reduced by 21% in the CA1‐3 area in comparison with nonstimulated controls, whereas a significant increase of 29% was found in the fascia dentata. Significant changes were no longer present at 4 weeks after the last generalized seizure. The observed changes in muscimol‐stimulated 36Cl− uptake at the FK stage closely parallel the recently observed changes in [3H]muscimol binding in the CA1 area and fascia dentata. These results indicate that kindling causes a transiently decreased GABAA receptor‐mediated function in the CA1‐3, in contrast to an increased GABAA receptor‐mediated function in the fascia dentata.

Cl− conduction of GABAA-receptor complex of synaptic membranes of rat brain cortex after development of chronic epileptization of the brain (pharmacological kindling)

“…The number of GABA A -receptors and their sensitivity also decreased. These results are consistent with the data obtained by other authorities on the models of pharmacological and electrostimulation kindling [10,12,13,15].…”

Long‐lasting increased excitability differs in dentate gyrus vs. CA1 in freely moving chronic epileptic rats after electrically induced status epilepticus

“…Whether the number of GABA A receptors in our post-SE model is increased in granule cells, as was observed after kindling epileptogenesis (Titulaer et al, 1995;Nusser et al, 1998), remains to be determined. In this respect, it is interesting that fEPSP responses …”

Dorsal Hippocampal Kindling Produces a Selective and Enduring Disruption of Hippocampally Mediated Behavior

“…DHPC kindling has been shown to produce changes in NMDA receptor currents (Mody, 1999) and changes in both inhibition and GABA A receptor characteristics (de Jonge and Racine, 1987;Titulaer et al, 1995;Mody, 1999) that last for 1 month or longer after kindling. Because these changes might be expected to alter the optimal physiological conditions for induction of intrahippocampal forms of plasticity, such as long-term potentiation, they could disrupt the strength, pattern, or effectiveness of plastic changes related to learning.…”