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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Muscarinic modulation of synaptic transmission in slices of the rat ventral striatum is dependent on the frequency of afferent stimulation. Pennartz, C.M.A.; Lopes da Silva, F.H.

Summary. The propagation of epileptiform burst activity was investigated in the CA1 area of the in-vitro hippocampal slice preparation of the guinea pig. This activity was provoked by 0.1 mM 4-aminopyridine in the bathing medium and was recorded in the pyramidal layer with an array of eight electrodes. The delay between the first population spike of a burst recorded with different electrodes was calculated using the cross-correlation function. The propagation velocity was estimated from the delays and the electrode intervals. It was found that the velocity of spontaneous and evoked epileptiform bursts varies between 0.15 and 5 m/s and is not confined to the range of conduction velocities of the fibre systems in CA 1 (0.3-0.55 and 1.0-1.8 m/s). Different velocities can be present in different parts of the CA1 area and the initiation of spontaneous bursts is not confined to the CA2-3 areas, but can also occur in CA1. Burst activity also propagated in a low calcium-high magnesium medium. Different mechanisms of propagation are discussed and it is argued that the propagation velocity due to ephaptic interaction may vary largely. It is concluded that epileptiform activity can be propagated not only by synaptic connections at or near the pyramidal layer, but also by way of electrical field effects of population spikes.

Kindling epileptogenesis was induced by periodic electrical stimulation of the Schaffer collateral/commissural pathway in the CA1 area of the rat hippocampus. The progressive nature of hippocampal kindling is demonstrated by a detailed description of the behavioral signs and the progressive increase of the after-discharge duration in the course of kindling acquisition. Furthermore, the evolution of the alterations in the paired-pulse local evoked field potentials and the modifications of the GABAA receptor binding and of the expression of mRNAs encoding for the subunits of the GABAA and glutamate receptors are considered. Evidence is presented that during kindling opposite changes occur in the CA1 and the fascia dentata in terms of the balance between excitation and inhibition due to contrasting changes in GABA-mediated inhibitory function.

Immunocytochemical techniques were used to study changes of GABA immunoreactivity in the rat hippocampal CA1 region during kindling epileptogenesis, gradually developing over a period of two weeks by daily electrical tetanization of Schaffer collaterals/commissural fibres. The number of GABA-immunoreactive somata per mm2 was quantified in CA1 region after 6 and 14 stimulus-induced afterdischarges and in fully kindled animals. The absolute values were compared with those obtained from controls and the relative difference between the side where the stimulations were applied and the contralateral side was determined. In comparison to controls the rats showed, after 6 afterdischarges at the ipsilateral, stimulated side, a slight increase in cell density of about 10%; after 14 afterdischarges, there was a significant increase of 38% together with an enhanced labelling density, while in fully kindled rats (34 afterdischarges) there was no significant difference with controls. At the contralateral side, we observed a different pattern of, respectively, a small decrease (17%), no significant difference, and a significant increase of 22% in fully kindled animals. This result is discussed in relation to observations that fully kindled rats, investigated 24 days after the last seizure of the acquisition phase, showed rather a significant decrease by 35% of cell density at the stimulated side and a regional loss of immunoreactivity of varicosities. At this point in time, no significant changes were found at the contralateral side. The complex time-course of GABA immunoreactivity during epileptogenesis consists of a transient increase in the early phase of kindling acquisition followed by a process of gradual reduction that leads to the long-term decrease of GABA immunoreactivity and high excitability.

Differential effects of elevated extracellular calcium on field potentials in dentate gyrus and CA1 of the rat hippocampal slice preparation Melchers, B.P.C.; Pennartz, C.M.A.; Lopes da Silva, F.H.