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
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.
Data availability
All data generated through this pipeline is continually available from web portal: http://marmoset.brainarchitecture.org/
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.
Reviewing Editor
- Moritz Helmstaedter, Max Planck Institute for Brain Research, Germany
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.
Version 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.
Metrics
-
- 5,006
- views
-
- 627
- downloads
-
- 47
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
A high-throughput neurohistological pipeline for brain-wide mesoscale connectivity mapping of the common marmoset
eLife 8:e40042.
https://doi.org/10.7554/eLife.40042
Further reading
-
- Neuroscience
Functional interactions between the prefrontal cortex and hippocampus, as revealed by strong oscillatory synchronization in the theta (6–11 Hz) frequency range, correlate with memory-guided decision-making. However, the degree to which this form of long-range synchronization influences memory-guided choice remains unclear. We developed a brain-machine interface that initiated task trials based on the magnitude of prefrontal-hippocampal theta synchronization, then measured choice outcomes. Trials initiated based on strong prefrontal-hippocampal theta synchrony were more likely to be correct compared to control trials on both working memory-dependent and -independent tasks. Prefrontal-thalamic neural interactions increased with prefrontal-hippocampal synchrony and optogenetic activation of the ventral midline thalamus primarily entrained prefrontal theta rhythms, but dynamically modulated synchrony. Together, our results show that prefrontal-hippocampal theta synchronization leads to a higher probability of a correct choice and strengthens prefrontal-thalamic dialogue. Our findings reveal new insights into the neural circuit dynamics underlying memory-guided choices and highlight a promising technique to potentiate cognitive processes or behavior via brain-machine interfacing.
-
- Neuroscience
Hippocampal place cells in freely moving rodents display both theta phase precession and procession, which is thought to play important roles in cognition, but the neural mechanism for producing theta phase shift remains largely unknown. Here, we show that firing rate adaptation within a continuous attractor neural network causes the neural activity bump to oscillate around the external input, resembling theta sweeps of decoded position during locomotion. These forward and backward sweeps naturally account for theta phase precession and procession of individual neurons, respectively. By tuning the adaptation strength, our model explains the difference between ‘bimodal cells’ showing interleaved phase precession and procession, and ‘unimodal cells’ in which phase precession predominates. Our model also explains the constant cycling of theta sweeps along different arms in a T-maze environment, the speed modulation of place cells’ firing frequency, and the continued phase shift after transient silencing of the hippocampus. We hope that this study will aid an understanding of the neural mechanism supporting theta phase coding in the brain.
