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Connectional architecture of a mouse hypothalamic circuit node controlling social behavior

Lo, Liching and Yao, Shenqin and Kim, Dong-Wook and Cetin, Ali and Harris, Julie and Zeng, Hongkui and Anderson, David J. and Weissbourd, Brandon (2019) Connectional architecture of a mouse hypothalamic circuit node controlling social behavior. Proceedings of the National Academy of Sciences of the United States of America, 116 (15). pp. 7503-7512. ISSN 0027-8424. PMCID PMC6462064. doi:10.1073/pnas.1817503116.

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Type 1 estrogen receptor-expressing neurons in the ventrolateral subdivision of the ventromedial hypothalamus (VMHvl^(Esr1)) play a causal role in the control of social behaviors, including aggression. Here we use six different viral-genetic tracing methods to systematically map the connectional architecture of VMHvl^(Esr1) neurons. These data reveal a high level of input convergence and output divergence (“fan-in/fan-out”) from and to over 30 distinct brain regions, with a high degree (∼90%) of bidirectionality, including both direct as well as indirect feedback. Unbiased collateralization mapping experiments indicate that VMHvl^(Esr1) neurons project to multiple targets. However, we identify two anatomically distinct subpopulations with anterior vs. posterior biases in their collateralization targets. Nevertheless, these two subpopulations receive indistinguishable inputs. These studies suggest an overall system architecture in which an anatomically feed-forward sensory-to-motor processing stream is integrated with a dense, highly recurrent central processing circuit. This architecture differs from the “brain-inspired,” hierarchical feed-forward circuits used in certain types of artificial intelligence networks.

Item Type:Article
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URLURL TypeDescription Information CentralArticle Paper
Kim, Dong-Wook0000-0002-5497-5853
Anderson, David J.0000-0001-6175-3872
Weissbourd, Brandon0000-0001-5422-3873
Additional Information:© 2019 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND). Contributed by David J. Anderson, December 12, 2018 (sent for review October 11, 2018; reviewed by Clifford B. Saper and Richard B. Simerly). PNAS published ahead of print March 21, 2019. We thank Dr. Miquel Chillón Rodriguez, Dr. Fan Wang, Dr. Liqun Luo, and Dr. Rachael Neve for providing CAV-cre, retrograde Lenti-cre, TRIO reagents, and retrograde HSV-fDIO-cre viruses, respectively, for pilot experiments; Dr. Lynn Enquist and the Center for Neuroanatomy with Neurotropic Viruses viral core center (Princeton University) for H129 recombinants; Dr. Kimberly Ritola of Janelia Research Campus for G-deleted EnvA rabies viruses; Bin Yang for help with cell-volume measurement software; Ben Ouellette for technical help; C. Chiu for laboratory management; and G. Mancuso for administrative assistance. This work was supported by NIH Grants MH070053, MH085082, and MH112593 (to D.J.A.). B.W. is a Howard Hughes Medical Institute Fellow of the Life Sciences Research Foundation. D.J.A. is an Investigator of the Howard Hughes Medical Institute. Author contributions: L.L., D.-W.K., D.J.A., and B.W. designed research; L.L. and D.-W.K. performed research; S.Y., A.C., J.H., and H.Z. contributed new reagents/analytic tools; L.L., D.-W.K., D.J.A., and B.W. analyzed data; and L.L., D.J.A., and B.W. wrote the paper. Reviewers: C.B.S., Harvard Medical School, Beth Israel Deaconess Medical Center; and R.B.S., Vanderbilt University. The authors declare no conflict of interest. This article contains supporting information online at
Funding AgencyGrant Number
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Life Sciences Research FoundationUNSPECIFIED
Subject Keywords:hypothalamus; aggression; social behavior; VMHvl; connectivity
Issue or Number:15
PubMed Central ID:PMC6462064
Record Number:CaltechAUTHORS:20181029-135550328
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Official Citation:Connectional architecture of a mouse hypothalamic circuit node controlling social behavior. Liching Lo, Shenqin Yao, Dong-Wook Kim, Ali Cetin, Julie Harris, Hongkui Zeng, David J. Anderson, Brandon Weissbourd. Proceedings of the National Academy of Sciences Apr 2019, 116 (15) 7503-7512; DOI: 10.1073/pnas.1817503116
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:90473
Deposited By: Tony Diaz
Deposited On:30 Oct 2018 01:48
Last Modified:01 Mar 2022 17:56

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