Summary: Researchers have created a 3D reconstruction of a marmoset brain that could help offer insights into human neural connectivity.
The ability to comprehensively map the architecture of connections between neurons in primate brains has long proven elusive for scientists. But a new study, conducted in Japan with contributing neuroscientists from Cold Spring Harbor Laboratory (CSHL), has resulted in a 3D reconstruction of a marmoset brain, as well as information about neuronal connectivity across the entire brain, that offers an unprecedented level of detail..
The study has introduced new methodology, combining experimental and computational approaches, that helps account for significant variation between individual brains. It allows for synthesizing unique brain connectivity maps into a single reference brain. The resulting data set for the marmoset brain is an ideal launching-off point for further studies, and scientists believe it may offer insights into human neural connectivity.
CSHL Professor Partha Mitra, who conceptualized and collaboratively led the study as part of Brain/MINDS research conducted at the RIKEN Center for Brain Science in Japan, explains that the endgame for any large-scale brain study is to learn more about human brain architecture and how disease can affect it. To do so, scientists must study a brain that is similar to a human’s.
The brain architecture of marmosets more closely resembles that of humans than does the mouse brain, which has been the focus of similar efforts in the past. While mice are currently the mainstay for modeling human disease, the emergence of marmoset models of human neurological disorders has made marmosets a target of new research.
Among primates, the marmosets’ relatively small brains lend themselves to thorough mapping of neural connections. And in comparison with extensively studied primates like the macaque, marmosets can be easier to study because their brain surfaces are flatter than the more folded cortical surfaces of larger primates.
The results of Mitra and colleagues’ new study are detailed in the journal eLife.
“Brain connectivity studies have been carried out in the marmoset before,” Mitra explains. “But we did not have complete three-dimensional digital data sets, showing connectivity patterns across several entire brains at the light-microscope resolution. The data we now have is completely unprecedented in scale and in information content.”
With this new data and approach as a basis, Mitra and other neuroscientists are one step closer to making sense of the complex neural connections in the primate–and human–brain. The hope is that this line of research will eventually lead to fundamental therapeutic advances for human diseases.
Funding: Brain Mapping of Integrated Neurotechnologies for Disease Studies (Brain/MINDS), Japan Agency for Medical Research and Development, AMED, Crick-Clay Professorship (CSHL), Mathers Foundation, H.N. Mahabala funded this study.
Source: Sara Roncero-Menendez – CSHL
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is credited to CSHL.
Original Research: Open access research for “A high-throughput neurohistological pipeline for brain-wide mesoscale connectivity mapping of the common marmoset” by 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, and Partha Mitra in eLife. Published February 5 2019.
A high-throughput neurohistological pipeline for brain-wide mesoscale connectivity mapping of the common marmoset
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.