The expression level of the mRNAs encoding the Flip and Flop versions of the AMPA-selective glutamate receptor subunits A, B, C and D was studied using in situ hybridization in the hippocampus of rats kindled by Schaffer collateral/commissural fibre stimulation. The expression levels of the Flip variant of GluR-A, B and C mRNAs were bilaterally enhanced in the dentate granule neurons of fully kindled animals 24 h after the last seizure. These changes were already observed after the sixth kindling stimulation (preconvulsive-stage), but not after a single afterdischarge. Four weeks after the last seizure, when the animals were still hypersensitive to kindling stimulations, only GluR-A Flip expression was enhanced. These results suggest that kindling epileptogenesis is accompanied by an increased number and enhanced sensitivity of the expressed AMPA type glutamate receptors in the fascia dentata, leading to an enhanced excitatory synaptic transmission which may contribute to the process of kindling epileptogenesis.

Expression of GABA-A receptor subunit in mRNAs in hippocampal pyramidal and granular neurons in the kindling model of epileptogenesis: an in situ hybridization study. Kamphuis, W.; de Rijk, T.C.; Lopes da Silva, F.H. Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Accepted 24 January 1995 AbstractTo investigate the molecular changes underlying kindling epileptogenesis in the rat hippocampus, the expression levels of the genes encoding for 13 different y-aminobutyric acid type-A receptor (GABAAR) subunits were measured in hippocampal principal neurons using in situ hybridization techniques and semi-quantitative analysis of the autoradiograms. Schaffer collateral-commissural pathway kindled rats were investigated at three different stages of kindling acquisition, at 24 h after the last seizure and at long-term (28 days) after termination of kindling stimulations. Changes were distinct for the different subunits in the three analyzed regions (CA1, CA3, fascia dentata) and also different for the various kindling stages. In all hippocampal areas at the early phases of kindling epileptogenesis, before the appearance of generalized seizures, an increase was found of those transcripts that constituted the majority of the expressed variants in control animals (al, a2, a4, /31, /32, /33, y2/y2L mRNA). In these stages, the increased levels of different variants in the granular neurons of the fascia dentata were more pronounced when compared to the pattern of changes in pyramidal cells of CA1 and CA3. In fully kindled animals, the expression levels of several subunits returned to control levels, whereas/33 and y2/y2L mRNA expression was still significantly enhanced in all areas. At long-term, few changes were encountered. The long-splice variant of 3,2 was decreased within pyramidal and granular neurons while the total level of y2 mRNA was not different from controls. The increased GABAAR subunit expression in the fascia dentata may underly the reported increased GABAAR ligand binding and the increased GABA mediated inhibition. However, the decreased GABAAR binding and the attenuation of GABAergic inhibition in CA1, could not be explained by a decrement of receptor subunit expression.

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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.