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A high-throughput neurohistological pipeline for brain-wide mesoscale connectivity mapping of the common marmoset

  1. Meng Kuan Lin  Is a corresponding author
  2. Yeonsook Shin Takahashi  Is a corresponding author
  3. Bing-Xing Huo
  4. Mitsutoshi Hanada
  5. Jaimi Nagashima
  6. Junichi Hata
  7. Alexander S Tolpygo
  8. Keerthi Ram
  9. Brian C Lee
  10. Michael I Miller
  11. Marcello GP Rosa
  12. Erika Sasaki
  13. Atsushi Iriki
  14. Hideyuki Okano
  15. Partha Mitra
  1. RIKEN, Japan
  2. Cold Spring Harbor Laboratory, United States
  3. Indian Institute of Technologies Madras, India
  4. Johns Hopkins University, United States
  5. Monash University, Australia
  6. Central Institute for Experimental Animals, Japan
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Cite this article as: eLife 2019;8:e40042 doi: 10.7554/eLife.40042

Abstract

Understanding the connectivity architecture of entire vertebrate brains is a fundamental but difficult task. Here we present an integrated neuro-histological pipeline as well as a grid-based tracer injection strategy for systematic mesoscale connectivity mapping in the common Marmoset (Callithrix jacchus). Individual brains are sectioned into ~1700 20µm sections using the tape transfer technique, permitting high quality 3D reconstruction of a series of histochemical stains (Nissl, myelin) interleaved with tracer labelled sections. Systematic in-vivo MRI of the individual animals facilitates injection placement into reference-atlas defined anatomical compartments. Further, combining the resulting 3D volumes, containing informative cytoarchitectonic markers, with in-vivo and ex-vivo MRI, and using an integrated computational pipeline, we are able to accurately map individual brains into a common reference atlas despite the significant individual variation. This approach will facilitate the systematic assembly of a mesoscale connectivity matrix together with unprecedented 3D reconstructions of brain-wide projection patterns in a primate brain.

Article and author information

Author details

  1. Meng Kuan Lin

    Laboratory for Marmoset Neural Architecture, Center for Brain Science, RIKEN, Wako, Japan
    For correspondence
    mengkuan.lin@riken.jp
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8191-8563
  2. Yeonsook Shin Takahashi

    Laboratory for Marmoset Neural Architecture, Center for Brain Science, RIKEN, Wako, Japan
    For correspondence
    yeonsook.takahashi@riken.jp
    Competing interests
    The authors declare that no competing interests exist.
  3. Bing-Xing Huo

    Laboratory for Marmoset Neural Architecture, Center for Brain Science, RIKEN, Wako, Japan
    Competing interests
    The authors declare that no competing interests exist.
  4. Mitsutoshi Hanada

    Laboratory for Marmoset Neural Architecture, Center for Brain Science, RIKEN, Wako, Japan
    Competing interests
    The authors declare that no competing interests exist.
  5. Jaimi Nagashima

    Laboratory for Marmoset Neural Architecture, Center for Brain Science, RIKEN, Wako, Japan
    Competing interests
    The authors declare that no competing interests exist.
  6. Junichi Hata

    Laboratory for Marmoset Neural Architecture, Center for Brain Science, RIKEN, Wako, Japan
    Competing interests
    The authors declare that no competing interests exist.
  7. Alexander S Tolpygo

    Department of Neuroscience, Cold Spring Harbor Laboratory, Cold Spring Harbor, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Keerthi Ram

    Department of Electrical Engineering, Indian Institute of Technologies Madras, Chennai, India
    Competing interests
    The authors declare that no competing interests exist.
  9. Brian C Lee

    Center for Imaging Science, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Michael I Miller

    Center for Imaging Science, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Marcello GP Rosa

    Department of Physiology and Biomedicine Discovery Institute, Monash University, Clayton, Australia
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6620-6285
  12. Erika Sasaki

    Department of Applied Developmental Biology, Central Institute for Experimental Animals, Tokyo, Japan
    Competing interests
    The authors declare that no competing interests exist.
  13. Atsushi Iriki

    Center for Biosystems Dynamics Research, RIKEN, Wako, Japan
    Competing interests
    The authors declare that no competing interests exist.
  14. Hideyuki Okano

    Laboratory for Marmoset Neural Architecture, Center for Brain Science, RIKEN, Wako, Japan
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7482-5935
  15. Partha Mitra

    Department of Neuroscience, Cold Spring Harbor Laboratory, Cold Spring Harbor, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8818-6804

Funding

Brain Mapping of Integrated Neurotechnologies for Disease Studies, Japan Agency for Medical Research and Development

  • Hideyuki Okano

Crick-Clay Professoeship

  • Partha Mitra

Mathers Foundation

  • Partha Mitra

H N Mahabala Chair

  • Partha Mitra

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. The funders is only expect the outcome of marmoset brain connectivity mapping using trace tracing studies.

Ethics

Animal experimentation: The experiment protocol was approved by the Research Resource Division (RRD) under (approval authorization H29-2-242(3)) from the support unit for animal resources development in conformity with Article 24 of the RIKEN regulations for animal experiments in Center for Brain Science, RIKEN. Each marmoset received multiple injections of fluorescent tracers using stereotaxic coordinates. All brain surgery was performed under isoflurane (2%)/alfaxan (100ul/dose) anesthesia and every effort was made to minimize suffering. Body temperature, heart rate, and SPO2 were continually monitored during surgery.

Reviewing Editor

  1. Moritz Helmstaedter, Max Planck Institute for Brain Research, Germany

Publication history

  1. Received: July 18, 2018
  2. Accepted: February 4, 2019
  3. Accepted Manuscript published: February 5, 2019 (version 1)

Copyright

© 2019, Lin et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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