Striatal output regulates the postnatal maturation of cortical circuits.

The dorsomedial prefrontal cortex (dmPFC) is interconnected with the basal ganglia (BG) through large-scale circuit loops that regulate critical motor and cognitive functions. In mice, these circuits undergo extensive postnatal maturation with marked changes in neural activity and expansion of synaptic connectivity. While cortical activity is known to regulate the development of downstream striatal circuits, the role of the basal ganglia in cortical maturation remains unknown. Here, we used mesoscale two-photon microscopy and whole-cell electrophysiology to examine whether striatal output during early postnatal development impacts the activity and maturation of upstream dmPFC circuits. We found that ablating spiny projection neurons of the direct or indirect pathways of the striatum during the first two postnatal weeks causes bidirectional changes in dmPFC neural activity, similar to observations in mature circuits. In addition, these manipulations alter the maturation of synaptic connectivity of dmPFC layer 2/3 pyramidal neurons, shifting the balance of excitation and inhibition of cortical circuits. These findings demonstrate that striatal output modulates the activity of cortical circuits during early postnatal development and suggest a regulatory role of the basal ganglia in the establishment of cortical circuits.