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  • 1
    ISSN: 1432-1106
    Keywords: Horizontal cells ; Hippocampus ; Morphology ; Electrophysiological properties ; Development ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In an ontogenetic study, combining morphological analysis and patch clamp recordings, a transiently appearing horizontal cell type was identified in the dentate gyrus. The cells were exclusively located in the outer third of the stratum moleculare. They were present at postnatal day 2 (P2) and could be identified with fluorescent dyes until around P14. The morphology was bipolar, with a putative axonal and a dendritic process stretching out parallel to the pial surface without any preferential direction. Patch clamp studies in the current and voltage clamp mode were performed in hippocampal slices on visually identified horizontal cells, between P4 and P7, which were subsequently stained with lucifer yellow. The cells had a low resting membrane potential, around — 55 mV. They were excitable, displaying broad action potentials (duration 3–20 ms) and, unlike mature dentate granule cells, they also expressed a strong delayed inward rectifier with properties reminiscent of the IQ current. Unlike granule cells, no postsynaptic signals could be observed during elevation of [K+]o or electrical stimulation, suggesting that the horizontal cells did not participate in functional hippocampal circuitry. We suggest that these cells represent migrating cells with subsequent differentiation to granule cells or inhibitory interneurons. Alternatively they may be part of the early radial glia or serve as transient target cells for afferent fibres between the entorhinal cortex and the dentate gyrus.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-1106
    Keywords: Acidosis ; Seizures ; Brain slices ; Rat
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Lowering [Mg2+]o induces epileptiform bursting in hippocampus and entorhinal cortex (EC), presumably by activation of N-methyl-d-aspartate (NMDA) receptors. Since increasing [H+]o has been shown to reduce NMDA receptor activation, we hypothesized that this could contribute to anticonvulsant actions of acidic pH. To test this, we studied the effects of raising extracellular PCO2 (20.6%, pH = 6.7) or lowering extracellular pH (6.7 or 6.2) on low-Mg2+-induced epileptiform discharges. Lowering the pH to 6.7 by either means increased the interval between seizure-like events (SLEs), decreased the maximal amplitude of SLEs, and, if the site of seizure generation was at a distance from the recording site, acidification slowed the rate of seizure propagation. In contrast, the duration of SLEs was unaffected by acidic pH or high PCO2. Raising PCO2 or lowering pH to 6.7 also blocked early (8–10 min) but not late (〉 20 min) phases of status-like discharges. All effects of the extracellular pH changes were fully reversible. Further lowering of extracellular pH to 6.2 completely and reversibly blocked both SLEs and status-like discharges. Our data show that the effects of high PCO2 and low pH on seizures in the EC in vitro may be dose-dependent and consistent with induction by proton blockade of NMDA receptors. Thus, blockade of NMDA currents by protons may be an important component of the anticonvulsant action of extracellular acidosis. The results also suggest that acidosis may be a desirable property for new antiepileptic treatments.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1912
    Keywords: Calcium ; Epileptiform activity ; Loreclezole ; Low magnesium ; Rat ; Entorhinal cortex-hippocampus slices
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Effects of loreclezole (R72063), a triazole derivative with anticonvulsant properties, were studied on field potentials in rat hippocampal slices and on different patterns of low Mg2+-induced epileptiform activity in combined entorhinal cortex-hippocampal slices. Lowering extracellular Mg2+ induced recurrent (10–60/min), short (40 – 80 ms) discharges in hippocampal areas CA1 and CA3. In the entorhinal cortex (EC) up to 90 s long ictaform events associated with large negative field potential and changes in the neuronal microenvironment were generated. These seizure like events changed their characteristics after one to two hours to recurrent discharges of 0.8 to 10 s. 20 μM loreclezole blocked the seizure like events in the entorhinal cortex completely 30–80 min after onset of application. The recurrent short discharges in the hippocampus were reliably blocked by 40 μM loreclezole 60 – 90 min after bath application with incomplete recovery after washout of several hours. The recurrent discharges in the entorhinal cortex were reliably blocked by 80 μM loreclezole applied for 80–100 min. Decreases in [Ca2+]0 and associated slow field potentials evoked by repetitive stimulation of the stratum radiatum were depressed in a dose dependent manner, while similar changes induced by alvear stimulation remained almost unaffected. A paired pulse stimulus paradigm used to test for effect of loreclezole on synaptically evoked transient field potentials in normal medium revealed interference with mechanisms involved in frequency potentiation. While responses to alvear stimulation were largely unaffected, the response to a paired pulse stimulus to stratum radiatum was depressed over the whole range of tested stimulus intervals (15 to 150 ms). The findings suggest that loreclezole has effects on different patterns of epileptiform activity induced by extracellular low Mg2+ possibly by interfering with processes leading to frequency potentiation.
    Type of Medium: Electronic Resource
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