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
Source 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.
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