Development and cadherin-mediated control of prefrontal corticostriatal projections in mice
Roxana E. Mesías,
Yosif Zaki,
Christopher A. Guevara,
Lauren G. Friedman,
Ayan Hussein,
Karen Therrien,
Alexandra R. Magee,
Nikolaos Tzavaras,
Pamela Del Valle,
Mark G. Baxter,
George W. Huntley,
Deanna L. Benson
Affiliations
Roxana E. Mesías
Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Yosif Zaki
Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Christopher A. Guevara
Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Lauren G. Friedman
Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Ayan Hussein
Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Karen Therrien
Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Alexandra R. Magee
Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Nikolaos Tzavaras
Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Pamela Del Valle
Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Graduate School of Biomedical Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Mark G. Baxter
Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Section on Comparative Medicine, Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA
George W. Huntley
Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA
Deanna L. Benson
Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Corresponding author
Summary: Action-outcome associations depend on prefrontal cortex (PFC) projections to the dorsal striatum. To assess how these projections form, we measured PFC axon patterning, synapse formation, and functional maturation in the postnatally developing mouse striatum. Using Hotspot analysis, we show that PFC axons form an adult-like pattern of clustered terminations in the first postnatal week that remains largely stable thereafter. PFC-striatal synaptic strength is adult-like by P21, while excitatory synapse density increases until adulthood. We then tested how the targeted deletion of a candidate adhesion/guidance protein, Cadherin-8 (Cdh8), from corticostriatal neurons regulates pathway development. Mutant mice showed diminished PFC axon targeting and reduced spontaneous glutamatergic synaptic activity in the dorsal striatum. They also exhibited impaired behavioral performance in action-outcome learning. The data show that PFC-striatal axons form striatal territories through an early, directed growth model and they highlight essential contributions of Cdh8 to the anatomical and functional features critical for the formation of action-outcome associations.
