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

Meng Kuan Lin, Yeonsook Shin Takahashi, Bing-Xing Huo, Mitsutoshi Hanada, Jaimi Nagashima, Junichi Hata, Alexander S. Tolpygo, Keerthi Ram, Brian C. Lee, Michael I. Miller, Marcello GP Rosa, Erika Sasaki, Atsushi Iriki, Hideyuki Okano, Partha Mitra
Published on eLife | Feb 5, 2019

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 20 µm sections using the tape transfer technique, permitting high quality 3D reconstruction of a series of histochemical stains (Nissl, myelin) interleaved with tracer labeled sections. Systematic in-vivo MRI of the individual animals facilitates injection placement into reference-atlas defined anatomical compartments. Further, by 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.