PT  - JOURNAL ARTICLE
AU  - Meng Kuan Lin
AU  - Yeonsook Shin Takahashi
AU  - Bing-Xing Huo
AU  - Mitsutoshi Hanada
AU  - Jaimi Nagashima
AU  - Junichi Hata
AU  - Alexander S. Tolpygo
AU  - Keerthi Ram
AU  - Brian Lee
AU  - Michael Miller
AU  - Marcello G.P. Rosa
AU  - Erika Sasaki
AU  - Atsushi Iriki
AU  - Hideyuki Okano
AU  - Partha P. Mitra
TI  - A High-throughput Neurohistological Pipeline for Brain-Wide Mesoscale Connectivity Mapping of the Common Marmoset
AID  - 10.1101/315804
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 315804
4099  - http://biorxiv.org/content/early/2018/05/08/315804.short
4100  - http://biorxiv.org/content/early/2018/05/08/315804.full
AB  - Understanding the connectivity architecture of entire vertebrate brains is a fundamental but difficult task. MRI based methods offer whole brain coverage, but remain indirect in the approach to connectivity mapping. Recent progress has been made in directly mapping whole-brain connectivity architecture in the mouse at the mesoscopic scale. The basic approach uses tracer injections systematically placed on a grid of locations spanning the brain and computational analysis of the resulting whole brain data sets. Scaling this approach to bigger primate brains poses nontrivial technical challenges. Here we present an integrated neurohistological 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. 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 overcome the significant individual variation exhibited by Marmosets to obtain routine and high quality maps to a common atlas framework. This will facilitate the systematic assembly of a mesoscale connectivity matrix together with unprecedented 3D reconstructions of brain-wide projection patterns in a primate brain. While component instruments or protocols may be available from previous work, we believe that this is the first detailed systems-level presentation of the methodology required for high-throughput neuroanatomy in a model primate.