A high-throughput neurohistological pipeline for brain-wide mesoscale connectivity mapping of the common marmoset
- RIKEN, Japan
- Cold Spring Harbor Laboratory, United States
- Indian Institute of Technologies Madras, India
- Johns Hopkins University, United States
- Monash University, Australia
- Central Institute for Experimental Animals, Japan
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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
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
- Moritz Helmstaedter, Max Planck Institute for Brain Research, Germany
Publication history
- Received: July 18, 2018
- Accepted: February 4, 2019
- Accepted Manuscript published: February 5, 2019 (version 1)
- Version of Record published: February 21, 2019 (version 2)
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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