Epileptiform events and kainate receptor activity changes considerably during entorhinal cortex development, an ex vivo study

Developmental Neuroscience

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Article / Publication Details Abstract

Epilepsy is a commonly diagnosed neurological disease, which often develops already in childhood. The prominent feature of this dysfunction is the strong, unprovoked hypersynchronous neuronal activity of the brain, especially in the cortex, which appears in recurrent seizures. Previous studies indicated potential modulatory role of kainate types of glutamate receptors in this mechanism. In our experiments, we used combined hippocampal-entorhinal rat brain slices of different ages. Developing (2-, 3-, 4-week-old), adolescent (6-week-old), and adult (3-month-old) groups were investigated. During the experiments, first we provoked convulsions by magnesium-free perfusion solution, then, to investigate the role of kainate receptors, seizure-like events were suppressed by applying a specific GluK1/2 antagonist (UBP-296). Neuronal network activity was recorded by multi electrode array (MEA chip), and temporal features of field potentials and single-cell activity were analysed in the different age groups. The frequency, duration of spontaneous events, the overall seizure characteristics and spike activities were compared. Spontaneous events were categorized into interictal epileptiform discharges (IED) and seizure-like events (SLE) on the basis of the temporal structure of activities. At 3- and 4-week-old animals IEDs were observable, which entirely disappeared after 4th weeks. The structure and the length of SLEs varied in the younger animals (3-, 4-week-old animals), however, after the 6th week, these events became more stabilized. In most groups, the count of detected spikes was significantly higher in layer II/III than in the layer V. The neuronal networks started to behave like adult ones at 4 weeks of age. The length of events decreased in adult animals due to the maturation of the network, and the inhibition becomes stronger. The IEDs disappeared completely and the SLEs became stable and stereotypic at the 6-weeks-old animals. UBP-296 administration reduced the number of IEDs however had no substantial effect on the SLEs.

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