Kindling alters entorhinal cortex-hippocampal interaction by increased efficacy of presynaptic GABA(B) autoreceptors in layer III of the entorhinal cortex.
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 microM) 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.
Gloveli
Tengis
T
Johannes-Müller-Institute of Physiology at the Charité, Humboldt University Berlin, Tucholskystr. 2, 10117, Berlin, Germany. tengis.gloveli@charite.de
Behr
Joachim
J
Dugladze
Tamar
T
Kokaia
Zaal
Z
Kokaia
Merab
M
Heinemann
Uwe
U
D000200:Action Potentials / Q000502:physiology; D000818:Animals; D017660:Autoreceptors / Q000502:physiology; D001418:Baclofen / Q000494:pharmacology; D004594:Electrophysiology; D018728:Entorhinal Cortex / Q000166:cytology / Q000502:physiology; D004833:Epilepsy, Temporal Lobe / Q000503:physiopathology; D018755:GABA Agonists / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D007150:Immunohistochemistry; D007696:Kindling, Neurologic / Q000502:physiology*; D023421:Models, Animal; D009433:Neural Inhibition / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000187:drug effects / Q000502:physiology*; D017661:Receptors, Presynaptic / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
D017660:Autoreceptors; D018755:GABA Agonists; D018080:Receptors, GABA-B; D017661:Receptors, Presynaptic; D001418:Baclofen