Striatal output regulates the postnatal maturation of cortical circuits

The dorsomedial prefrontal cortex (dmPFC) and basal ganglia (BG) are tightly interconnected through cortico-BG-thalamocortical (CBGT) loops that undergo extensive refinement during postnatal development. While the role of cortical activity in shaping striatal circuit maturation is well established, the extent to which the BG regulate dmPFC development remains unclear. Here, we examined whether early striatal output influences the maturation of dmPFC activity and connectivity. Targeted ablation of direct or indirect pathway spiny projection neurons during the first two postnatal weeks induced bidirectional changes in dmPFC neural activity akin to BG modulation of cortical dynamics observed in mature circuits. Interestingly, these manipulations also disrupted synaptic maturation of layer 2/3 pyramidal neurons, shifting the balance between excitation and inhibition. Together, these findings demonstrate that striatal output regulates cortical activity during early postnatal development and suggest a previously unrecognized role for the BG in guiding the establishment of prefrontal cortical networks.