RT Journal Article
SR Electronic
T1 Transcriptional signatures of connectomic subregions of the human striatum
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 089458
DO 10.1101/089458
A1 Linden Parkes
A1 Ben Fulcher
A1 Murat Yücel
A1 Alex Fornito
YR 2016
UL http://biorxiv.org/content/early/2016/12/11/089458.abstract
AB Functionally distinct regions of the brain are thought to possess a characteristic connectional fingerprint – a profile of incoming and outgoing connections that defines the function of that area. This observation has motivated efforts to subdivide cortical and subcortical areas using their patterns of connectivity. However, it remains unclear whether these connectomically-defined subregions of the brain can be distinguished at the molecular level. Here, we combine high-resolution diffusion-weighted magnetic resonance imaging with comprehensive transcriptomic data to show that connectomically-defined subregions of the striatum carry distinct transcriptional signatures. Using data-driven clustering of diffusion tractography, seeded from the striatum, in 100 healthy individuals, we identify a tripartite organization of the caudate and putamen that comprises ventral, dorsal, and caudal subregions. We then use microarray data of gene expression levels in 19 343 genes, taken from 98 tissue samples distributed throughout the striatum, to accurately discriminate the three connectomically-defined subregions with 80-90% classification accuracy using linear support vector machines. This classification accuracy was robust at the group and individual level. Genes contributing strongly to the classification were enriched for gene ontology categories including dopamine signaling, glutamate secretion, response to amphetamine, and metabolic pathways, and were implicated in risk for disorders such as schizophrenia, autism, and Parkinson’s disease. Our findings highlight a close link between regional variations in transcriptional activity and interregional connectivity in the brain, and suggest that there may be a strong genomic signature of connectomically-defined subregions of the brain.