Striatal output regulates the postnatal maturation of cortical circuits

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 esta...

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Main Authors: 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
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:Cell Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2211124725009581
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author 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
author_facet 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
author_sort Michael Janeček
collection DOAJ
description 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.
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publishDate 2025-09-01
publisher Elsevier
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series Cell Reports
spelling doaj-art-f3053b3c90c34415b3fee8bacd360fa62025-08-25T04:14:21ZengElsevierCell Reports2211-12472025-09-0144911618710.1016/j.celrep.2025.116187Striatal output regulates the postnatal maturation of cortical circuitsMichael Janeček0Tara Deemyad1Yi-Chun Shih2Vicente Valle3Andrew D’Agostino4Michael Matarazzo5Megan S. Perez6Kyle D. Ketchesin7Susana da Silva8Rui T. Peixoto9Department of Psychiatry, University of Pittsburgh, 450 Technology Dr., Pittsburgh, PA 15219, USA; Center for Neuroscience at the University of Pittsburgh, Pittsburgh, PA, USADepartment of Psychiatry, University of Pittsburgh, 450 Technology Dr., Pittsburgh, PA 15219, USADepartment of Psychiatry, University of Pittsburgh, 450 Technology Dr., Pittsburgh, PA 15219, USA; Center for Neuroscience at the University of Pittsburgh, Pittsburgh, PA, USADepartment of Ophthalmology, University of Pittsburgh, 1622 Locust St., Pittsburgh, PA 15219, USADepartment of Psychiatry, University of Pittsburgh, 450 Technology Dr., Pittsburgh, PA 15219, USADepartment of Psychiatry, University of Pittsburgh, 450 Technology Dr., Pittsburgh, PA 15219, USADepartment 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, USADepartment of Psychiatry, University of Pittsburgh, 450 Technology Dr., Pittsburgh, PA 15219, USA; Center for Neuroscience at the University of Pittsburgh, Pittsburgh, PA, USADepartment of Ophthalmology, University of Pittsburgh, 1622 Locust St., Pittsburgh, PA 15219, USA; Department of Bioengineering, Swanson School of Engineering, University of Pittsburgh, Pittsburgh, PA, USADepartment of Psychiatry, University of Pittsburgh, 450 Technology Dr., Pittsburgh, PA 15219, USA; Center for Neuroscience at the University of Pittsburgh, Pittsburgh, PA, USA; Corresponding authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2211124725009581CP: Neuroscience
spellingShingle 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
Striatal output regulates the postnatal maturation of cortical circuits
Cell Reports
CP: Neuroscience
title Striatal output regulates the postnatal maturation of cortical circuits
title_full Striatal output regulates the postnatal maturation of cortical circuits
title_fullStr Striatal output regulates the postnatal maturation of cortical circuits
title_full_unstemmed Striatal output regulates the postnatal maturation of cortical circuits
title_short Striatal output regulates the postnatal maturation of cortical circuits
title_sort striatal output regulates the postnatal maturation of cortical circuits
topic CP: Neuroscience
url http://www.sciencedirect.com/science/article/pii/S2211124725009581
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