Genetic and informatic resources for multi-scale brain research

The mammalian brain is a highly complex system with levels of organization that extend from nucleotides to large networks that generate adaptive behavior. To test our understanding of brain function we need to assemble and model interactions across levels. We are doing this for a genetically diverse family of BXD strains. This family has been densely genotyped and phenotyped for thousands of brain-related behavioral, cellular, and molecular traits making this population particularly amenable to multi-scale analysis. Here we provide an example of this type of analysis starting with a well defined trait-cholinergic interneuron number in the dorsal striatum. We show strong associations between cholinergic neuron numbers and alcohol and drug response phenotypes among the BXD population and map part of the variation in coexpression to chromosomes1 and 12. Polymorphisms in Lrfn5 may be responsible for trait variation that maps to the chromosome 12 locus.