Kindling alters entorhinal cortex-hippocampal interaction by increased efficacy of presynaptic GABA b autoreceptors in layer III of the entorhinal cortex

Abstract

We studied the effect of kindling, a model of temporal lobe epilepsy, on the frequency-dependent information transfer from the entorhinal cortex to the hippocampus in vitro. In control rats repetitive synaptic activation of layer III projection cells resulted in a frequency dependent depression of the synaptic transfer of action potentials to the hippocampus. One-to-two-days after kindling this effect was strongly reduced. Although no substantial change in synaptic inhibition upon single electrical stimulation was detected in kindled rats, there was a significant depression in the prolonged inhibition following high frequency stimulation. In kindled animals, paired-pulse depression (PPD) of stimulus-evoked IPSCs in layer III neurons was significantly stronger than in control rats. The increase of PPD is most likely caused by an increased presynaptic GABA B receptor-mediated autoinhibition. In kindled animals activation of presynaptic GABA B receptors by baclofen (10 μM) suppressed monosynaptic IPSCs significantly more than in control rats. In contrast, activation of postsynaptic GABA B receptors by baclofen was accompanied by comparable changes of the membrane conductance in both animal groups. Thus, in kindled animals activation of the layer III-CA1 pathway is facilitated by an increased GABA B receptor-mediated autoinhibition leading to an enhanced activation of the monosynaptic EC-CA1 pathway.