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Integration of gene expression and brain-wide connectivity reveals the multiscale organization of mouse hippocampal networks
Open accessAbstract
Understanding the organization of the hippocampus is fundamental to understanding brain function related to learning, memory, emotions, and diseases such as Alzheimer's disease. Physiological studies in humans and rodents have suggested that there is both structural and functional heterogeneity along the longitudinal axis of the hippocampus. However, the recent discovery of discrete gene expression domains in the mouse hippocampus has provided the opportunity to re-evaluate hippocampal connectivity. To integrate mouse hippocampal gene expression and connectivity, we mapped the distribution of distinct gene expression patterns in mouse hippocampus and subiculum to create the Hippocampus Gene Expression Atlas (HGEA). Notably, previously unknown subiculum gene expression patterns revealed a hidden laminar organization. Guided by the HGEA, we constructed the most detailed hippocampal connectome available using Mouse Connectome Project ( http://www.mouseconnectome.org ) tract tracing data. Our results define the hippocampus' multiscale network organization and elucidate each subnetwork's unique brain-wide connectivity patterns.
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“In rodents, DG and CA3 contribute primarily to intrahippocampal connectivity (working to integrate information within the hippocampus), while CA1/CA2 and subiculum are organized into global networks tasked with extrahippocampal communication12.”
From Dysregulation of adult hippocampal neuroplasticity in major depression: Pathogenesis and therapeutic implications (2022) · cites this paper as [12]
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“This prediction is highly consistent with the currently known interareal connections of HPF, providing a level of validation to the transcriptomic cell type framework”
From A taxonomy of transcriptomic cell types across the isocortex and hippocampal formation (2021) · cites this paper as Bienkowski et al., 2018
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Metadata
- Authors
- Bienkowski, M. S., Bowman, I., Song, M. Y., Gou, L., Ard, T., Cotter, K., Zhu, M., Benavidez, N. L., Yamashita, S., Abu-Jaber, J., Azam, S., Lo, D., Foster, N. N., Hintiryan, H., & Dong, H.-W.
- Affiliations
- University of Southern California (US)
- Corresponding author
- Bienkowski, Michael S.
- Dong, Hong-Wei
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2018-10-08
- Volume
- 21
- Issue
- 11
- Pages
- 1628-1643
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC6398347
- OpenAlex
- W2895709954
- Cited by
- 224
- References
- 58
- Citations by year
- 2026: 17 · 2025: 35 · 2024: 33 · 2023: 25 · 2022: 29 · 2021: 31 · 2020: 36 · 2019: 16 · 2018: 1
- FWCI
- 12.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (P50AG005142)
- National Institute of Mental Health (U19MH114821, F32MH107071, R01MH094360, U01MH114829, RF1MH114112)
- National Cancer Institute (U01CA198932)
- National Institute on Deafness and Other Communication Disorders (R01DC008983)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- hippocampus, hippocampal subiculum, gene expression domains, laminar organization, neural tracing, mouse brain atlas
- MeSH terms
- Animals, Brain, Hippocampus, Nerve Net, Neural Pathways, Neurons, Gene Expression, Mice, Connectome
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