The formation of functionally different areas in the cerebral cortex results from a timely regulated interaction between intrinsic genetic mechanisms and electrical activity. However, whether and how transcriptional regulation influences spontaneous activity intrinsic to the neocortex during critical periods of corticogenesis is poorly elucidated. In the lab, we use mice deficient for cortical Nr2f1 (also known as COUP-TFI) to investigate how a genetic-determinant of somatosensory area-identity linked to epileptic encephalopathy, influences immature neural excitability and network activity generated within the neocortex. Our research unveiled that loss of Nr2f1 alters intrinsic excitability and morphological features of pyramidal neurons during early postnatal stages. We also identified voltage-gated ion channels regulated by Nr2f1 during a critical time window of somatosensory area specification. Accordingly, Nr2f1 loss impacted on spontaneous network activity and synchronization at perinatal stages.

Together, our data suggest that genetic specification of cortical area identity relies on intrinsic bioelectrical properties regulating patterns of spontaneous activity intrinsic to the neocortex early on in cortical development.