Large scale digital atlases in neuroscience

Abstract

The increasing availability of genome wide data sets promise to shed light into the etiology and pathophysiology of genetically complex disorders, including substance abuse and dependence. Since the development of its flagship project of a genome wide image-based atlas of themouse brain, the Allen Institute for Brain Science has produced several large-scale digital atlases including atlases of the developing and adult human brain. Recent work from our group has shown local neighborhood relationships between fine anatomical subdivisions that are associated with discrete neuronal subtypes and genes involved with synaptic transmission. Importantly, regional enrichment for synaptic elements, including genes involved in dopaminergic signaling, is conserved among multiple human subjects. However, substantial structural variation in gene expression persists throughout the brain, suggesting highly organized gene networks underlying neuroanatomy. Specific patterns of expression important to brain function, disease conditions, and differences across species have been identified. For example, calbindin 1 (CALB1) demonstrates an expression pattern unique to human hippocampus in comparison to mouse and rhesus monkeys. Recent additions to the resources at the Allen Institute for Brain Science include a mesoscale atlas of mouse connectivity and non-human primatemacaque monkey. These newer resources can help establish precise quantitativemaps for the neuroscience community.We will present an overview of our research pertaining to the Allen Institute atlases and tools highlighting applications for researchers in the genetics of addiction.