Striatal output regulates the postnatal maturation of cortical circuits
Michael Janeček,
Tara Deemyad,
Yi-Chun Shih,
Vicente Valle,
Andrew D’Agostino,
Michael Matarazzo,
Megan S. Perez,
Kyle D. Ketchesin,
Susana da Silva,
Rui T. Peixoto
Affiliations
Michael Janeček
Department of Psychiatry, University of Pittsburgh, 450 Technology Dr., Pittsburgh, PA 15219, USA; Center for Neuroscience at the University of Pittsburgh, Pittsburgh, PA, USA
Tara Deemyad
Department of Psychiatry, University of Pittsburgh, 450 Technology Dr., Pittsburgh, PA 15219, USA
Yi-Chun Shih
Department of Psychiatry, University of Pittsburgh, 450 Technology Dr., Pittsburgh, PA 15219, USA; Center for Neuroscience at the University of Pittsburgh, Pittsburgh, PA, USA
Vicente Valle
Department of Ophthalmology, University of Pittsburgh, 1622 Locust St., Pittsburgh, PA 15219, USA
Andrew D’Agostino
Department of Psychiatry, University of Pittsburgh, 450 Technology Dr., Pittsburgh, PA 15219, USA
Michael Matarazzo
Department of Psychiatry, University of Pittsburgh, 450 Technology Dr., Pittsburgh, PA 15219, USA
Megan S. Perez
Department of Psychiatry, University of Pittsburgh, 450 Technology Dr., Pittsburgh, PA 15219, USA; Department of Human Genetics, School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
Kyle D. Ketchesin
Department of Psychiatry, University of Pittsburgh, 450 Technology Dr., Pittsburgh, PA 15219, USA; Center for Neuroscience at the University of Pittsburgh, Pittsburgh, PA, USA
Susana da Silva
Department of Ophthalmology, University of Pittsburgh, 1622 Locust St., Pittsburgh, PA 15219, USA; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USA
Rui T. Peixoto
Department of Psychiatry, University of Pittsburgh, 450 Technology Dr., Pittsburgh, PA 15219, USA; Center for Neuroscience at the University of Pittsburgh, Pittsburgh, PA, USA; Corresponding author
Summary: 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.
