Dendritic anomalies in a freezing model of microgyria: a parametric study

Despite easier recognition of focal developmental cortical anomalies with modern morphological and functional imaging techniques, mechanisms leading to refractory epilepsy are still poorly understood. Recent experimental studies have shown that not only the lesioned cortex, but also the apparently normal adjacent cortex undergoes morphological changes and alterations of its neuronal connections. To further investigate the modifications of the cortex surrounding a focal maldevelopmental lesion, we applied a freezing insult to newborn rat cortex, resulting in a focal cortical malformation similar to human microgyria. Corticocortical associative neurons were retrogradely labeled in a Golgi-like fashion using biotinylated dextran amine combined with NMDA. In addition to previously reported alterations, a considerable spine loss was observed in the basal dendrites of neurons located in the eulaminated cortex adjacent to the lesion. These data demonstrate profound maldevelopmental alterations which are not limited to the macroscopically abnormal lesion, but extend at a cellular level to the surrounding cortex. The observed alterations may contribute to the increased excitability of the cortex harboring a microgyric lesion as well as the frequently associated cognitive impairment.