Excitability changes in freeze-induced neocortical microgyria

Abstract 

A freezing probe was placed on the skull of postnatal day (PN) 1 rats to induce formation of a cerebrocortical microsulcus. Experimental studies were performed on PN days 21–24. At that time point, Nissl-stained sections revealed the presence of a microsulcus similar to that described in human dysplastic cortex. Immunocytochemical staining for parvalbumin, calretinin and calbindin indicated a significant decrease in the number of immunoreactive neurons within the microsulcus and non-significant decreases in regions adjacent to the microsulcus. Staining for the glial markers GFAP and vimentin was increased near the microsulcus. Using in vitro brain slices, recordings were made in cortex adjacent to the microsulcus. Epileptiform activity was observed in response to electrical stimulation near the microsulcus. Analysis of the voltage dependence of evoked epileptiform discharges suggested the presence of an inhibitory component. As previously observed in non-lesioned animals, bath application of 4-aminopyridine induced bicuculline-sensitive spontaneous burst discharges in the presence of excitatory amino acid antagonists. These results suggest that cortical freeze lesions associated with abnormal neuronal migration produce a chronic hyperexcitable state. The findings are consistent with a mechanism involving an alteration, not loss, of inhibition in this model.

Keywords:  Microgyria, Neocortex, Development, Epileptogenesis, Inhibition