The importance of circuit considerations for differentially characterizing disorders such as major depression, anxiety, and obsessive–compulsive disorders, and substance (including nicotine) addiction is beginning to be recognized. These illnesses are considered disorders of the affective circuitry underlying emotion and motivated behaviors, which spans the brainstem, hypothalamus, frontal and cingulate cortices, and basal cortical nuclei.
We propose a concerted experimental effort to comprehensively determine brainwide mesoscale neuronal connectivity in model organisms. Our proposal is to employ existing neuroanatomical methods, including tracer injections and viral gene transfer, which have been sufficiently well-established and are appropriately scalable for deployment at this level. The first and primary objective is to apply these methods in a standardized, high-throughput experimental program to fully map the mesoscale wiring diagram for the mouse brain and, following the model of successful genome projects, to rapidly make the results and digitized primary data publicly accessible. The second objective is to collate and, where possible, digitize existing experimental data from the macaque, and to pursue targeted experiments using standardized protocols to plug key gaps in our knowledge of primate brain connectivity. Additionally, we argue for similar efforts in other model organisms and for the pursuit of experimental methods that can be used in postmortem human brain tissue.
For as little as a few million dollars ranging up to perhaps $20 million, depending on the redundancy in coverage that we commit to researchers could get a detailed mammal brain map.
The full dataset will comprise hundreds of terabytes - a very modest data-storage burden, according to Mitra. "That will give us about twofold coverage of the entire brain circuit in a first draft, and could be accomplished in two or three years, with cooperation from the neuroscience community. At more robust funding levels, we could attempt 10-fold coverage over, perhaps, a five-year period." In the spirit of genome projects, all data from the proposed program would be made rapidly available over the web to the entire research community.
While the immediate focus now is to bring a mouse connectivity project to fruition, the authors also make the case for cataloging and digitizing results from existing studies in other species, and for filling key gaps with targeted studies. Moreover, there is an important need, they argue, for further development and validation of experimental techniques that can be used directly in the human brain.