Relationships between Gene Expression and Brain Wiring in the Adult Rodent Brain

Abstract

We studied the global relationship between gene expression and neuroanatomical connectivity in the adult rodent brain. We utilized a large data set of the rat brain “connectome” from the Brain Architecture Management System (942 brain regions and over 5000 connections) and used statistical approaches to relate the data to the gene expression signatures of 17,530 genes in 142 anatomical regions from the Allen Brain Atlas. Our analysis shows that adult gene expression signatures have a statistically significant relationship to connectivity. In particular, brain regions that have similar expression profiles tend to have similar connectivity profiles, and this effect is not entirely attributable to spatial correlations. In addition, brain regions which are connected have more similar expression patterns. Using a simple optimization approach, we identified a set of genes most correlated with neuroanatomical connectivity, and find that this set is enriched for genes involved in neuronal development and axon guidance. A number of the genes have been implicated in neurodevelopmental disorders such as autistic spectrum disorder. Our results have the potential to shed light on the role of gene expression patterns in influencing neuronal activity and connectivity, with potential applications to our understanding of brain disorders. Supplementary data are available at http://www.chibi.ubc.ca/ABAMS.

Author Summary

We tested the idea that the “wiring diagram” of the adult brain has a relationship with where genes are expressed. We were inspired by similar work carried out by groups examining the nematode worm Caenorhabditis elegans. By using large-scale databases of brain connectivity and gene expression in rodents, we found that many genes involved in the development of the brain show correlations with anatomical connectivity patterns. Some of the genes we found have been implicated in disorders such as autism, which is suspected to affect brain wiring. While the biological causes of the patterns we found are not yet known, we believe they provide new insight into the patterns of gene expression in the brain and will spur further study of this problem.