BRAIN CONNECTS: Comprehensive regional projection map of marmoset with single axon and cell type resolution - SUMMARY
This ambitious proposal will establish an integrated experimental-computational platform to create the first
comprehensive brain-wide mesoscale connectivity map in a non-human primate, the common marmoset
(Callithrix jacchus),. It will do so by tracing axonal projections of RNA barcode-identified neurons brain-wide in
the marmoset, utilizing a sequencing-based imaging method that also permits simultaneous transcriptomic cell
typing of the identified neurons. This will help bridge the gap between brain-wide mesoscale connectivity data
available for the mouse from a decade of mapping efforts using modern techniques and the absence of
comparable data in humans and NHP.
The proposal will bring together new viral barcode-based approaches with established tracer-injection based
methods to collect an unprecedented data set which will permit comprehensive mapping of region-to-region
axonal projections in the marmoset brain with cell-type specificity, apply this data to scientific questions regarding
how brain connectivity differs between primates and rodents, address the relation between MRI-derived
measures to ground-truth connectivity, and utilize web-based tools to engage the research community in
annotating and using the resulting data. A diverse team of world-leading experts and pioneers in the problem
domain who are already collaborating, spanning diverse institutions and disciplines, and equipped with
outstanding facilities and resources, will come together to assemble the enabling platform. There are five specific
aims to achieve stated goals. Aim 1 is to establish data acquisition platform for mesoscale projection mapping
in marmoset using barcoded + fluorescent AAV/AAV-retro. Aim 2 is to develop brain-wide single-axon projection
maps using systemic injections with simultaneous transcriptomic cell-typing. Aim 3 is to develop data
management and analysis pipelines. Aim 4 is to perform comparative studies of the mesoscale connectivity in
marmoset and mouse, comparing MRI-based connectivity with ground truth. Aim 5 is to develop platforms for
data dissemination, community engagement through web portal, collaborative proofreading and annotations.
Such a data set will have profound scientific significance, comparable to the first whole genome map of a primate.
As genomes encode the blueprint for understanding an organism’s phenotype, so does the architecture of brain
circuitry contain the blueprint for explaining an animal’s behavior and holds the key to many open questions.
