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Experience-dependent plasticity in an innate social behavior is mediated by hypothalamic LTP

Stagkourakis, Stefanos and Spigolon, Giada and Liu, Grace and Anderson, David J. (2020) Experience-dependent plasticity in an innate social behavior is mediated by hypothalamic LTP. Proceedings of the National Academy of Sciences of the United States of America, 117 (41). pp. 25789-25799. ISSN 0027-8424. PMCID PMC7568289.

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All animals can perform certain survival behaviors without prior experience, suggesting a “hard wiring” of underlying neural circuits. Experience, however, can alter the expression of innate behaviors. Where in the brain and how such plasticity occurs remains largely unknown. Previous studies have established the phenomenon of “aggression training,” in which the repeated experience of winning successive aggressive encounters across multiple days leads to increased aggressiveness. Here, we show that this procedure also leads to long-term potentiation (LTP) at an excitatory synapse, derived from the posteromedial part of the amygdalohippocampal area (AHiPM), onto estrogen receptor 1-expressing (Esr1⁺) neurons in the ventrolateral subdivision of the ventromedial hypothalamus (VMHvl). We demonstrate further that the optogenetic induction of such LTP in vivo facilitates, while optogenetic long-term depression (LTD) diminishes, the behavioral effect of aggression training, implying a causal role for potentiation at AHiPM→VMHvl^(Esr1) synapses in mediating the effect of this training. Interestingly, ∼25% of inbred C57BL/6 mice fail to respond to aggression training. We show that these individual differences are correlated both with lower levels of testosterone, relative to mice that respond to such training, and with a failure to exhibit LTP after aggression training. Administration of exogenous testosterone to such nonaggressive mice restores both behavioral and physiological plasticity. Together, these findings reveal that LTP at a hypothalamic circuit node mediates a form of experience-dependent plasticity in an innate social behavior, and a potential hormone-dependent basis for individual differences in such plasticity among genetically identical mice.

Item Type:Article
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URLURL TypeDescription Information Paper CentralArticle
Stagkourakis, Stefanos0000-0003-1218-791X
Spigolon, Giada0000-0002-1704-8372
Liu, Grace0000-0003-0159-6750
Anderson, David J.0000-0001-6175-3872
Additional Information:© 2020 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, August 25, 2020 (sent for review June 9, 2020; reviewed by Robert C. Malenka and Richard Mooney). PNAS first published September 24, 2020. We thank Dr. B. Weissbourd and Dr. L. Li for advice on experiments, Dr. Y. Ouadah and Dr. P. Williams for advice during writing of the manuscript, X. Da and J. S. Chang for technical assistance, X. Da and C. Chiu for laboratory management, and G. Mancuso for administrative support. Members of the D.J.A. laboratory are thanked for discussion during the preparation of this manuscript. Confocal imaging was performed in the Biological Imaging Facility, with the support of the Caltech Beckman Institute and the Arnold and Mabel Beckman Foundation. This study was supported by NIH Grant R01 MH070053 (to D.J.A.) and the European Molecular Biology Organization Advanced Long-Term Fellowship 736-2018 (to S.S.). D.J.A. is an investigator of the HHMI. Data Availability: All data discussed in the paper are available in the main text and SI Appendix. We used standard MATLAB functions and publicly available software indicated in the manuscript for analysis. Author contributions: S.S., G.S., and D.J.A. designed research; S.S. and G.S. performed research; S.S., G.S., G.L., and D.J.A. analyzed data; and S.S., G.S., and D.J.A. wrote the paper. Reviewers: R.C.M., Stanford University School of Medicine; and R.M., Duke University. The authors declare no competing interest. This article contains supporting information online at
Group:Tianqiao and Chrissy Chen Institute for Neuroscience
Funding AgencyGrant Number
Caltech Beckman InstituteUNSPECIFIED
Arnold and Mabel Beckman FoundationUNSPECIFIED
NIHR01 MH070053
European Molecular Biology Organization (EMBO)ALTF 736-2018
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Subject Keywords:innate behaviors; long-term potentiation; ventromedial hypothalamus; testosterone
Issue or Number:41
PubMed Central ID:PMC7568289
Record Number:CaltechAUTHORS:20200723-122438626
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Official Citation:Experience-dependent plasticity in an innate social behavior is mediated by hypothalamic LTP. Stefanos Stagkourakis, Giada Spigolon, Grace Liu, David J. Anderson. Proceedings of the National Academy of Sciences Oct 2020, 117 (41) 25789-25799; DOI: 10.1073/pnas.2011782117
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:104530
Deposited By: George Porter
Deposited On:24 Jul 2020 14:15
Last Modified:29 Oct 2020 17:20

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