Abstract

Different cortical areas are organized into distinct intracortical subnetworks. The manner in which descending pathways from the entire cortex interact subcortically as a network remains unclear. We developed an open-access comprehensive mesoscale mouse cortico-striatal projectome: a detailed connectivity projection map from the entire cerebral cortex to the dorsal striatum or caudoputamen (CP) in rodents. On the basis of these projections, we used new computational neuroanatomical tools to identify 29 distinct functional striatal domains. Furthermore, we characterized different cortico-striatal networks and how they reconfigure across the rostral–caudal extent of the CP. The workflow was also applied to select cortico-striatal connections in two different mouse models of disconnection syndromes to demonstrate its utility for characterizing circuitry-specific connectopathies. Together, our results provide the structural basis for studying the functional diversity of the dorsal striatum and disruptions of cortico-basal ganglia networks across a broad range of disorders.

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Acknowledgements

The authors are grateful to L.W. Swanson and H. Karten for serving on the Advisory Council for the Mouse Connectome Project (http://www.mouseconnectome.org/). This work was supported by NIH/NIMH MH094360-01A1 (H.-W.D.), NIH/NCI U01CA198932-01 (H.-W.D.), the CHDI Foundation A-7601 (H.-W.D.), NIH/NIMH U01MH106008 (X.W.Y.) and LONIR P41 EB015922 (A.W.T.).

Author information

Author notes

    • Houri Hintiryan
    •  & Nicholas N Foster

    These authors contributed equally to this work.

Affiliations

  1. USC Stevens Neuroimaging and Informatics Institute, Laboratory of Neuro Imaging (LONI), Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

    • Houri Hintiryan
    • , Nicholas N Foster
    • , Ian Bowman
    • , Maxwell Bay
    • , Monica Y Song
    • , Lin Gou
    • , Seita Yamashita
    • , Michael S Bienkowski
    • , Muye Zhu
    • , Arthur W Toga
    •  & Hong-Wei Dong
  2. Zilkha Neurogenetic Institute, Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

    • Brian Zingg
    •  & Hong-Wei Dong
  3. Center for Neurobehavioral Genetics, Semel Institute for Neuroscience & Human Behavior, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California, USA.

    • X William Yang
  4. Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California, USA.

    • Jean C Shih
  5. Department of Neurology, Keck School of Medicine of University of Southern California, Los Angeles, California, USA.

    • Hong-Wei Dong

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Contributions

H.-W.D. and H.H. conceived, designed and managed the entire project, conducted manual analysis of the raw data, and, along with N.N.F., prepared the manuscript and figures. N.N.F., along with H.H., H.-W., I.B., M.B. and M.S.B., refined and finalized the applied methods of analyses. I.B. led the informatics team and, along with M.B. and M.Z., created and executed all aspects of the informatics workflow and wrote the corresponding methods. B.Z. and L.G. made tracer injections and conducted subsequent tissue processing and imaging, M.Y.S. processed raw images in preparation for uploading to iConnectome, and S.Y. managed iConnectome for both raw image uploads and connectivity map displays. N.N.F. managed and conducted experiments pertaining to zQ175 and MAO knockout mice. X.W.Y. contributed his expertise regarding discussion of striatal function under normal and diseased conditions. J.C.S. provided the MAO A/B knockout mice and contributed to the interpretation of the data resulting from those subjects. A.W.T. served as project advisor. H.-W.D. conceived and led the Mouse Connectome Project. All of the authors offered constructive guidance for the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Houri Hintiryan or Hong-Wei Dong.

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    List of repeated cortical injections

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DOI

https://doi.org/10.1038/nn.4332