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Multimodal Analysis of Cell Types in a Hypothalamic Node Controlling Social Behavior
Open accessAbstract
The ventrolateral subdivision of the ventromedial hypothalamus (VMHvl) contains ∼4,000 neurons that project to multiple targets and control innate social behaviors including aggression and mounting. However, the number of cell types in VMHvl and their relationship to connectivity and behavioral function are unknown. We performed single-cell RNA sequencing using two independent platforms-SMART-seq (∼4,500 neurons) and 10x (∼78,000 neurons)-and investigated correspondence between transcriptomic identity and axonal projections or behavioral activation, respectively. Canonical correlation analysis (CCA) identified 17 transcriptomic types (T-types), including several sexually dimorphic clusters, the majority of which were validated by seqFISH. Immediate early gene analysis identified T-types exhibiting preferential responses to intruder males versus females but only rare examples of behavior-specific activation. Unexpectedly, many VMHvl T-types comprise a mixed population of neurons with different projection target preferences. Overall our analysis revealed that, surprisingly, few VMHvl T-types exhibit a clear correspondence with behavior-specific activation and connectivity.
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“In hypothalamus, several studies using either of the two approaches in mice demonstrate that activated neurons during a specific behavioral state are often distributed across a range of transcriptomic cell types (Kim et al., 2019; Moffitt et al., 2018; Xu et al., 2020).”
From What is a cell type and how to define it? (2022) · cites this paper as Kim et al., 2019
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“Indeed, in the ventromedial hypothalamus, few transcriptionally defined cell types exhibited a clear correspondence with behavior-specific activation or connectivity.”
From Classification of midbrain dopamine neurons using single-cell gene expression profiling approaches (2020) · cites this paper as [99]
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Metadata
- Authors
- Kim, D.-W., Yao, Z., Graybuck, L. T., Kim, T. K., Nguyen, T. N., Smith, K. A., Fong, O., Yi, L., Koulena, N., Pierson, N., Shah, S., Lo, L., Pool, A.-H., Oka, Y., Pachter, L., Cai, L., Tasic, B., Zeng, H., & Anderson, D. J.
- Affiliations
- California Institute of Technology (US)
- Allen Institute for Brain Science (US)
- Corresponding author
- Anderson, David J.
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2019-10
- Volume
- 179
- Issue
- 3
- Pages
- 713-728.e17
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC7534821
- OpenAlex
- W2981201615
- Cited by
- 259
- References
- 102
- Citations by year
- 2026: 25 · 2025: 40 · 2024: 33 · 2023: 42 · 2022: 43 · 2021: 32 · 2020: 41 · 2019: 3
- FWCI
- 9.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- CaltechAUTHORS (California Institute of Technology) (submittedVersion)
- Funders
- California Institute of Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Neuroendocrine regulation and behavior
- Keywords
- ventromedial hypothalamus, hypothalamic neurons, social behavior, aggression, mounting behavior, neuronal cell types, axonal projections, sexual dimorphism, intruder response, immediate early genes, single-cell transcriptomics, canonical correlation analysis, seqFISH
- MeSH terms
- Animals, Female, Hypothalamus, Male, Mice, Inbred BALB C, Mice, Inbred C57BL, Neurons, Sexual Behavior, Animal, Social Behavior, Estrogen Receptor alpha, Mice, Single-Cell Analysis, Transcriptome
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