Circuit and molecular architecture of a ventral hippocampal network
Open accessAbstract
The ventral hippocampus (vHPC) is a critical hub in networks that process emotional information. While recent studies have indicated that ventral CA1 (vCA1) projection neurons are functionally dissociable, the basic principles of how the inputs and outputs of vCA1 are organized remain unclear. Here, we used viral and sequencing approaches to define the logic of the extended vCA1 circuit. Using high-throughput sequencing of genetically barcoded neurons (MAPseq) to map the axonal projections of thousands of vCA1 neurons, we identify a population of neurons that simultaneously broadcast information to multiple areas known to regulate the stress axis and approach-avoidance behavior. Through molecular profiling and viral input-output tracing of vCA1 projection neurons, we show how neurons with distinct projection targets may differ in their inputs and transcriptional signatures. These studies reveal new organizational principles of vCA1 that may underlie its functional heterogeneity.
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This predicted isocortex-like circuit organization is highly consistent with currently known interareal connections of HPF, providing validation to the transcriptomic cell type framework.
“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 Gergues et al., 2020
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featureCounts: an efficient general purpose program for assigning sequence reads to genomic features
Liao, Y., Smyth, G. K., & Shi, W. (2014) · Bioinformatics · doi:10.1093/bioinformatics/btt656 · Cited by 27,219 · see citing works
HTSeq—a Python framework to work with high-throughput sequencing data
Anders, S., Pyl, P. T., & Huber, W. (2015) · Bioinformatics · doi:10.1093/bioinformatics/btu638 · Cited by 21,464 · see citing works
Metascape provides a biologist-oriented resource for the analysis of systems-level datasets
Zhou, Y., Zhou, B., Pache, L., Chang, M., Khodabakhshi, A. H., Tanaseichuk, O., Benner, C., & Chanda, S. K. (2019) · Nature Communications · doi:10.1038/s41467-019-09234-6 · Cited by 14,611 · see citing works
Complex heatmaps reveal patterns and correlations in multidimensional genomic data
Gu, Z., Eils, R., & Schlesner, M. (2016) · Bioinformatics · doi:10.1093/bioinformatics/btw313 · Cited by 10,122 · see citing works
Are the Dorsal and Ventral Hippocampus Functionally Distinct Structures?
Fanselow, M. S., & Dong, H.-W. (2010) · Neuron · doi:10.1016/j.neuron.2009.11.031 · Cited by 3,358 · see citing works
Thorndike, R. L. (1953) · Psychometrika · doi:10.1007/bf02289263 · Cited by 2,102 · see citing works
JACOBSON, L., & SAPOLSKY, R. (1991) · Endocrine Reviews · doi:10.1210/edrv-12-2-118 · Cited by 1,739 · see citing works
A Designer AAV Variant Permits Efficient Retrograde Access to Projection Neurons
Tervo, D. G. R., Hwang, B., Viswanathan, S., Gaj, T., Lavzin, M., Ritola, K., Lindo, S. E., Michael, S. C., Кулешова, Е. П., Ojala, D. S., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.09.021 · Cited by 1,170 · see citing works
Application of a translational profiling approach for the comparative analysis of CNS cell types
Doyle, J. P., Dougherty, J. D., Heiman, M., Schmidt, E. F., Stevens, T. R., Ma, G., Bupp, S., Shrestha, P., Shah, R. D., Doughty, M. L., et al. (2008) · Cell · doi:10.1016/j.cell.2008.10.029 · Cited by 912 · see citing works
Reduced fear expression after lesions of the ventral hippocampus
Kjelstrup, K. G., Tuvnes, F. A., Steffenach, H.-A., Murison, R., Moser, E. I., & Moser, M.-B. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.152112399 · Cited by 912 · see citing works
Viral-genetic tracing of the input-output organization of a central noradrenaline circuit
Schwarz, L. A., Miyamichi, K., Gao, X. J., Beier, K. T., Weissbourd, B., DeLoach, K. E., Ren, J., Ibanes, S., Malenka, R. C., Kremer, E. J., et al. (2015) · Nature · doi:10.1038/nature14600 · Cited by 744 · see citing works
Synaptic and Behavioral Profile of Multiple Glutamatergic Inputs to the Nucleus Accumbens
Britt, J. P., Benaliouad, F., McDevitt, R. A., Stuber, G. D., Wise, R. A., & Bonci, A. (2012) · Neuron · doi:10.1016/j.neuron.2012.09.040 · Cited by 716 · see citing works
Differential Control of Learning and Anxiety along the Dorsoventral Axis of the Dentate Gyrus
Kheirbek, M. A., Drew, L. J., Burghardt, N. S., Costantini, D. O., Tannenholz, L., Ahmari, S. E., Zeng, H., Fenton, A. A., & Hen, R. (2013) · Neuron · doi:10.1016/j.neuron.2012.12.038 · Cited by 713 · see citing works
Self-citationDiverging neural pathways assemble a behavioural state from separable features in anxiety
Kim, S.-Y., Adhikari, A., Lee, S. Y., Marshel, J. H., Kim, C. K., Mallory, C. S., Lo, M., Pak, S., Mattis, J., Lim, B. K., et al. (2013) · Nature · doi:10.1038/nature12018 · Cited by 666 · see citing works
Lebow, M. A., & Chen, A. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.1 · Cited by 660 · see citing works
Cenquizca, L. A., & Swanson, L. W. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.05.002 · Cited by 640 · see citing works
Anxiety Cells in a Hippocampal-Hypothalamic Circuit
Jimenez, J., Su, K., Goldberg, A., Luna, V. M., Biane, J. S., Ordek, G., Zhou, P., Ong, S. K., Wright, M. A., Zweifel, L. S., et al. (2018) · Neuron · doi:10.1016/j.neuron.2018.01.016 · Cited by 606 · see citing works
Self-citationBLA to vHPC inputs modulate anxiety-related behaviors
Felix-Ortiz, A. C., Beyeler, A., Seo, C., Leppla, C. A., Wildes, C. P., & Tye, K. M. (2013) · Neuron · doi:10.1016/j.neuron.2013.06.016 · Cited by 592 · see citing works
Cullinan, W. E., Herman, J. P., & Watson, S. J. (1993) · Journal of Comparative Neurology · doi:10.1002/cne.903320102 · Cited by 541 · see citing works
Cell type–specific genetic and optogenetic tools reveal hippocampal CA2 circuits
Kohara, K., Pignatelli, M., Rivest, A. J., Jung, H.-Y., Kitamura, T., Suh, J., Frank, D., Kajikawa, K., Mise, N., Obata, Y., et al. (2014) · Nature Neuroscience · doi:10.1038/nn.3614 · Cited by 528 · see citing works
Padilla-Coreano, N., Bolkan, S. S., Pierce, G. M., Blackman, D. R., Hardin, W. D., Garcia-Garcia, A. L., Spellman, T. J., & Gordon, J. A. (2016) · Neuron · doi:10.1016/j.neuron.2016.01.011 · Cited by 463 · see citing works
High-throughput mapping of single-neuron projections by sequencing of barcoded RNA
Kebschull, J. M., Garcia da Silva, P., Reid, A. P., Peikon, I. D., Albeanu, D. F., & Zador, A. M. (2016) · Neuron · doi:10.1016/j.neuron.2016.07.036 · Cited by 376 · see citing works
Selective information routing by ventral hippocampal CA1 projection neurons
Ciocchi, S., Passecker, J., Malagon‐Vina, H., Mikuš, N., & Klausberger, T. (2015) · Science · doi:10.1126/science.aaa3245 · Cited by 344 · see citing works
The logic of single-cell projections from visual cortex
Han, Y., Kebschull, J. M., Campbell, R. A. A., Cowan, D., Imhof, F., Zador, A. M., & Mrsic‐Flogel, T. D. (2018) · Nature · doi:10.1038/nature26159 · Cited by 310 · see citing works
Reward behaviour is regulated by the strength of hippocampus–nucleus accumbens synapses
LeGates, T. A., Kvarta, M. D., Tooley, J. R., Francis, T. C., Lobo, M. K., Creed, M. C., & Thompson, S. M. (2018) · Nature · doi:10.1038/s41586-018-0740-8 · Cited by 290 · see citing works
Distinct Hippocampal Pathways Mediate Dissociable Roles of Context in Memory Retrieval
Xu, C., Krabbe, S., Gründemann, J., Botta, P., Fadok, J. P., Osakada, F., Saur, D., Grewe, B. F., Schnitzer, M. J., Callaway, E. M., et al. (2016) · Cell · doi:10.1016/j.cell.2016.09.051 · Cited by 277 · see citing works
High-Throughput Mapping of Long-Range Neuronal Projection Using In Situ Sequencing
Chen, X., Sun, Y.-C., Zhan, H., Kebschull, J. M., Fischer, S., Matho, K. S., Huang, Z. J., Gillis, J. A., & Zador, A. M. (2019) · Cell · doi:10.1016/j.cell.2019.09.023 · Cited by 273 · see citing works
Heterogeneity within classical cell types is the rule: lessons from hippocampal pyramidal neurons
Cembrowski, M. S., & Spruston, N. (2019) · Nature Reviews Neuroscience · doi:10.1038/s41583-019-0125-5 · Cited by 258 · see citing works
Parfitt, G. M., Nguyen, R., Bang, J. Y., Aqrabawi, A. J., Tran, M. M., Seo, D. K., Richards, B. A., & Kim, J. C. (2017) · Neuropsychopharmacology · doi:10.1038/npp.2017.56 · Cited by 229 · see citing works
Hsu, D. T., Kirouac, G. J., Zubieta, J.-K., & Bhatnagar, S. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00073 · Cited by 228 · see citing works
Bienkowski, M. S., Bowman, I., Song, M. Y., Gou, L., Ard, T., Cotter, K., Zhu, M., Benavidez, N. L., Yamashita, S., Abu-Jaber, J., et al. (2018) · Nature Neuroscience · doi:10.1038/s41593-018-0241-y · Cited by 224 · see citing works
Neurogranin/RC3 Enhances Long-Term Potentiation and Learning by Promoting Calcium-Mediated Signaling
Huang, K., Huang, F. L., Jäger, T., Li, J., Reymann, K. G., & Balschun, D. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.2213-04.2004 · Cited by 197 · see citing works
Bipartite graphs in systems biology and medicine: a survey of methods and applications
Pavlopoulos, G. A., Kontou, P. I., Pavlopoulou, A., Bouyioukos, C., Markou, E., & Bagos, P. G. (2018) · GigaScience · doi:10.1093/gigascience/giy014 · Cited by 189 · see citing works
Miyakawa, T., Yared, E., Pak, J. H., Huang, F. L., Huang, K., & Crawley, J. N. (2001) · Hippocampus · doi:10.1002/hipo.1092 · Cited by 178 · see citing works
Analysis of direct hippocampal cortical field CA1 axonal projections to diencephalon in the rat
Cenquizca, L. A., & Swanson, L. W. (2006) · The Journal of Comparative Neurology · doi:10.1002/cne.20985 · Cited by 157 · see citing works
Hippocampal-Prefrontal Theta Transmission Regulates Avoidance Behavior
Padilla-Coreano, N., Canetta, S., Mikofsky, R. M., Alway, E., Passecker, J., Myroshnychenko, M., Garcia‐García, Á. L., Warren, R., Teboul, E., Blackman, D. R., et al. (2019) · Neuron · doi:10.1016/j.neuron.2019.08.006 · Cited by 138 · see citing works
Molecular Profiling of Neurons Based on Connectivity
Ekstrand, M. I., Nectow, A. R., Knight, Z. A., Latcha, K. N., Pomeranz, L. E., & Friedman, J. M. (2014) · Cell · doi:10.1016/j.cell.2014.03.059 · Cited by 137 · see citing works
Jin, J., & Maren, S. (2015) · Scientific Reports · doi:10.1038/srep08388 · Cited by 133 · see citing works
Kim, W. B., & Cho, J.-H. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.3579-16.2017 · Cited by 131 · see citing works
Ascending granule cell axon: An important component of cerebellar cortical circuitry
Gundappa-Sulur, G., Schutter, E. D., & Bower, J. M. (1999) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19990614)408:4 · Cited by 127 · see citing works
Besnard, A., Gao, Y., Kim, M. T., Twarkowski, H., Reed, A. K., Langberg, T., Feng, W., Xu, X., Saur, D., Zweifel, L. S., et al. (2019) · Nature Neuroscience · doi:10.1038/s41593-018-0330-y · Cited by 94 · see citing works
Coordinated Reductions in Excitatory Input to the Nucleus Accumbens Underlie Food Consumption
Reed, S. J., Lafferty, C. K., Mendoza, J. A., Yang, A. K., Davidson, T. J., Grosenick, L., Deisseroth, K. A., & Britt, J. P. (2018) · Neuron · doi:10.1016/j.neuron.2018.07.051 · Cited by 85 · see citing works
Huang, L., Kebschull, J. M., Fürth, D., Musall, S., Kaufman, M. T., Churchland, A. K., & Zador, A. M. (2020) · Cell · doi:10.1016/j.cell.2020.05.029 · Cited by 84 · see citing works
Three axonal projection routes of individual pyramidal cells in the ventral CA1 hippocampus
Arszovszki, A., Borhegyi, Z., & Klausberger, T. (2014) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2014.00053 · Cited by 73 · see citing works
Wang, Q., Jin, J., & Maren, S. (2016) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2016.04.002 · Cited by 70 · see citing works
Glangetas, C., Massi, L., Fois, G. R., Jalabert, M., Girard, D., Diana, M., Yonehara, K., Roska, B., Xu, C., Lüthi, A., et al. (2017) · Nature Communications · doi:10.1038/ncomms14456 · Cited by 56 · see citing works
Biased Connectivity of Brain-wide Inputs to Ventral Subiculum Output Neurons
Wee, R. W. S., & MacAskill, A. F. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.02.093 · Cited by 54 · see citing works
Association of the gene encoding neurogranin with schizophrenia in males
Ruano, D., Aulchenko, Y. S., Macedo, A., Soares, M. J., Valente, J., Azevedo, M. H., Hutz, M. H., Gama, C. S., Lobato, M. I. R., Belmonte-de-Abreu, P. S., et al. (2006) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2006.10.008 · Cited by 52 · see citing works
Rapid, experience-dependent translation of neurogranin enables memory encoding
Jones, K. J., Templet, S., Zemoura, K., Kuźniewska, B., Pena, F. X., Hwang, H., Ding, L. J., Haensgen, H., Nguyen, S. J., Saenz, C., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1716750115 · Cited by 39 · see citing works
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Miele, V., Matias, C., Robin, S. S., & Dray, S. (2019) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1007434 · Cited by 30 · see citing works
Hallock, H. L., Quillian, H. M., Maynard, K. R., Mai, Y., Chen, H.-Y., Hamersky, G. R., Shin, J. H., Maher, B. J., Jaffe, A. E., & Martinowich, K. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2020.04.014 · Cited by 25 · see citing works
Thomas, E., Burock, D., Knudsen, K., Deterding, E., & Yadin, E. (2013) · Neuroscience Letters · doi:10.1016/j.neulet.2013.05.078 · Cited by 23 · see citing works
Nine Quick Tips for Analyzing Network DataPreprint
Robin, S., Miele, V., Matias, C., et al. (2019) · arXiv (Cornell University) · doi:10.48550/arxiv.1904.05334 · Cited by 3 · see citing works
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Huang, L., Kebschull, J. M., Fürth, D., Musall, S., Kaufman, M. T., Churchland, A. K., & Zador, A. M. (2018) · Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) · doi:10.1101/422477 · Cited by 3 · see citing works
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A taxonomy of transcriptomic cell types across the isocortex and hippocampal formation
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- Authors
- Gergues, M. M., Han, K. J., Choi, H. S., Brown, B., Clausing, K. J., Turner, V. S., Vainchtein, I. D., Molofsky, A. V., & Kheirbek, M. A.
- Affiliations
- University of California, San Francisco (US)
- Harvard University (US)
- Corresponding author
- Kheirbek, Mazen A.
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2020-09-14
- Volume
- 23
- Issue
- 11
- Pages
- 1444-1452
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC7606799
- OpenAlex
- W3086890576
- Cited by
- 158
- References
- 54
- Citations by year
- 2026: 21 · 2025: 24 · 2024: 41 · 2023: 25 · 2022: 24 · 2021: 18 · 2020: 4 · 2019: 1
- FWCI
- 9.54
- Type
- journal article
- Language
- en
- Update notices
- correction (2021-09-22)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- U.S. Department of Health & Human Services | NIH | National Institute of Mental Health (R01 MH111754, R01 MH117961)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- ventral hippocampus, ventral CA1, projection neurons, neural circuit organization, axonal projections, stress axis, approach-avoidance behavior, emotional processing, gene expression signatures, neuronal heterogeneity, viral tracing
- MeSH terms
- Animals, Brain, Female, Male, Mice, Inbred C57BL, Neural Pathways, Neurons, Gene Expression Profiling, CA1 Region, Hippocampal
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