A key question about making any map concerns its scale, which determines its level of detail. At the finest scale of individual synapses and processes of every neuron, the brain shows a great deal of variability from individual to individual. At the macroscopic level, gross brain compartments such as the cerebellum or lobes of the cerebral cortex are too large to be nodes on a brainwide circuit map because they contain many sub-compartments. However, there exists a nontrivial "mesoscopic" scale, intermediate between these two levels that has been studied classically by neuroanatomists and is suitable for a meaningful circuit map.
"At the mesoscopic scale, neuroanatomists have found that there are well-defined regions -- hundreds of them -- and the circuitry we will be mapping is that between these regions," says Mitra. "This mesoscopic circuit is probably encoded within the species genome and is grown during brain development. Parts of this mesoscopic circuitry may be altered from its normal state in neuropsychiatric disorders."
While the current lack of a circuit diagram at the whole-brain level is "arguably the biggest knowledge gap in contemporary neuroscience," according to Mitra, this first phase of the project is but the prelude to another no less fundamental in importance. "The second phase will be to compare a number of model mice bearing genetic mutations, to see how connectivity in their brains compares with that of the 'reference' map," explained Mitra. "There is a parallel here with the Human Genome Project. The determination of a reference genome enabled genome-wide scans of mutations corresponding to disease phenotypes. In this case, we want to see how the brain-wide connectivity map is altered in the mice with mutations associated with neurol
|Contact: Peter Tarr|
Cold Spring Harbor Laboratory