Gene expression links functional networks across cortex and striatum
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The human brain is comprised of a complex web of functional networks that link anatomically distinct regions. However, the biological mechanisms supporting network organization remain elusive, particularly across cortical and subcortical territories with vastly divergent cellular and molecular properties. Here, using human and primate brain transcriptional atlases, we demonstrate that spatial patterns of gene expression show strong correspondence with limbic and somato/motor cortico-striatal functional networks. Network-associated expression is consistent across independent human datasets and evolutionarily conserved in non-human primates. Genes preferentially expressed within the limbic network (encompassing nucleus accumbens, orbital/ventromedial prefrontal cortex, and temporal pole) relate to risk for psychiatric illness, chloride channel complexes, and markers of somatostatin neurons. Somato/motor associated genes are enriched for oligodendrocytes and markers of parvalbumin neurons. These analyses indicate that parallel cortico-striatal processing channels possess dissociable genetic signatures that recapitulate distributed functional networks, and nominate molecular mechanisms supporting cortico-striatal circuitry in health and disease.
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More recent work has examined whole-brain distribution of OXTR genes against a limited set of genes and overexpression in broad functional brain networks, but researchers have yet to explore OXTR's associations with all protein-coding genes or with gene expression patterns associated with specific cognitive states.
“While more recent work has exclusively examined whole-brain distribution of OXTR genes against a limited set of genes13 and overexpression in broad functional brain networks (e.g., limbic network)14, researchers have yet to explore OXTR’s associations with all protein-coding genes or with gene expression patterns associated with specific cognitive states.”
From Oxytocin pathway gene networks in the human brain (2019) · cites this paper as [14]
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Zhang, J., Abiose, O., Katsumi, Y., Touroutoglou, A., Dickerson, B. C., & Barrett, L. F. (2019) · Scientific Reports · doi:10.1038/s41598-019-51793-7 · Cited by 47 · see citing works
- Authors
- Anderson, K. M., Krienen, F. M., Choi, E. Y., Reinen, J. M., Yeo, B. T. T., & Holmes, A. J.
- Affiliations
- Yale University (US)
- Harvard University (US)
- Stanford University (US)
- National University of Singapore (SG)
- Corresponding author
- Holmes, Avram J.
- ORCID
- Venue
- Nature Communications
- Published
- 2018-04-12
- Volume
- 9
- Issue
- 1
- Pages
- 1428-1428
- ISSN
- 2041-1723 (ISSN-L)
- PMC
- PMC5897339
- OpenAlex
- W2797660976
- Cited by
- 138
- References
- 88
- Citations by year
- 2026: 10 · 2025: 17 · 2024: 18 · 2023: 12 · 2022: 20 · 2021: 23 · 2020: 22 · 2019: 12 · 2018: 4
- FWCI
- 9.07
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Nature Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- National University of Singapore (submittedVersion, cc-by)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Science Foundation (1122492)
- Massachusetts General Hospital
- Yale University
- Harvard University
- Ministry of Earth Sciences
- Ministry of Education, India
- National Institutes of Health
- National Medical Research Council (CBRG14nov007)
- National Institute of Mental Health (K01MH099232)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- gene expression, limbic network, nucleus accumbens, prefrontal cortex, temporal pole, chloride channels, somatostatin neurons, parvalbumin neurons, oligodendrocytes, primate brain evolution, human brain
- MeSH terms
- Adult, Animals, Atlases as Topic, Autopsy, Female, Humans, Macaca, Male, Middle Aged, Nerve Net, Neural Pathways, Neurons, Nucleus Accumbens, Oligodendroglia, Parvalbumins, Somatostatin, Temporal Lobe, Biomarkers, Gene Expression, Prefrontal Cortex, Chloride Channels, Gene Expression Profiling
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