Development of early postnatal inhibitory function in the mouse medial prefrontal and primary somatosensory cortex

Abstract The prefrontal cortex (PFC) is characterized by protracted maturation that extends until adulthood. The cellular mechanisms controlling the early development of prefrontal circuits are still largely unknown. Our study delineates the developmental cellular processes that are on-going in the mouse medial PFC (mPFC) during the second and third postnatal weeks and compares them to those in the barrel cortex (BC). We show that basal synaptic transmission decreases from the second to the third postnatal week in both brain areas due to increased spontaneous inhibitory currents and reduced excitatory ones. Moreover, the GABAergic interneurons in the neonatal mPFC exhibit immature active properties. Furthermore, increasing GABAA receptor (GABAAR) activity leads to increased basal synaptic response and spontaneous activity of neonatal mPFC, but not BC. Additionally, the K-Cl co-transporter 2 (KCC2) expression is decreased in the neonatal mPFC compared to the pre-juvenile one as well as to the neonatal and pre-juvenile BC, suggesting that GABAAR function in the neonatal mPFC is depolarizing. Therefore, our study reveals two significant differences in the maturation of GABAergic function of mPFC compared to BC: a developmental delay in the depolarizing function of GABA and the immature active properties of GABAergic interneurons.