The effects of kindling on GABA-Mediated inhibition in the dentate gyrus of the rat. I. Paired-pulse depression

Expression of GABAA receptor subunit mRNAs in hippocampal pyramidal and granular neurons in the kindling model of epileptogenesis: an in situ hybridization study

“…In CA1 area of the hippocampus, experimental evidence has been found in support of this hypothesis; a reduction of inhibitory synaptic transmission takes place in the course of kindling as shown by a reduced pairedpulse inhibition of local evoked field potentials [22,24,26,77,78], a diminished sensitivity of the pyramidal neurons for iontophoretically applied GABA [20] and a reduced binding of the GABA A receptor agonist [3H]muscimol [69] and of benzodiazepines [29,67]. In sharp contrast to the decreased inhibition in CA1, in the fascia dentata paired pulse inhibition is enhanced [7,21,26,70,79], together with an increase in the amplitude of miniature inhibitory postsynaptic currents [53], and a robust increase in both [3H]muscimol and [3H]flunitrazepam binding in this area [51,62,67,69]. The results of these studies imply local differences in the response of the GABAergic inhibition to kindling stimulations, specifically an impaired inhibition in CA1-3 area, leading to an increased propensity for seizures, along with a strengthened inhibition in fascia dentata, possibly limiting seizure activity.…”

“…changes in GABAAR binding [29,51,62,67,69], in synaptic GABAergic inhibition [7,21,24,70,75,[77][78][79], in sensitivity for iontophoretically applied GABA [19] and in GABAAR mediated C1-uptake in synaptoneurosomes [66]. In this respect, it is of particular interest to compare the opposite changes in CA1-3 area, where a reduced GABAergic inhibition is manifested, with the changes in fascia dentata region where inhibition is strengthened [21,26,66,67,69,79].…”

“…Since these subunits are dominant under normal conditions it can be concluded that there is no conspicuous change induced by kindling of the overall subunit composition of GABAARs. Moreover, the relative increases of the different a type subunits are comparable, suggesting no striking alteration in the pharmacological profile of benzodiazepine modulation in the fascia dentata [13,39,[57][58][59]63,72] [51,62,[67][68][69], the increased GABAR mediated CI-uptake by synaptoneurosomes prepared from fascia dentata [66] and the gradual strengthening of local recurrent inhibition in the course of kindling [7,21,26,53,70,79]. At long-term the changes in inhibition, receptor binding and in GABA-mediated flux had virtually subsided and the expression of GABAAR subunits also returned to control levels.…”

GABAA receptor β1–3 subunit gene expression in the hippocampus of kindled rats

“…way leads to a gradual increase of the GABAergic inhibition in the fascia dentata [7,23,28] whereas in CA1 inhibition decreases [6,7,9,27]. These opposite changes in GABAergic inhibition are accompanied by a bilateral increased binding of GABAA-receptor agonist [3H]muscimol in the fascia dentata [14,18,22] and a decreased binding in CA1 [22].…”

“…In CA1 area, a reduction of the inhibition takes place as evidenced by a reduced paired-pulse inhibition of local evoked field potentials [7,9,27], a decreased sensitivity of the pyramidal neurons for iontophoretically applied GABA [6], and a reduced binding of the GABAA receptor agonist [3H]muscimol [22]. In contrast to the decreased inhibiton in CA1, in the fascia dentata pairedpulse inhibition is strengthened [7,23,28], together with a robust increase in [3H]muscimol binding in this area [14,18,22]. Structurally, the GABAA-receptor is a hetero-oligomeric complex composed of several subunits (ct, fl, ~,, ~, p), each of which exists in the brain in different variants [11,16].…”