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Distinct hypothalamic control of same- and opposite-sex mounting behaviour in mice

Karigo, Tomomi and Kennedy, Ann and Yang, Bin and Liu, Mengyu and Tai, Derek and Wahle, Iman A. and Anderson, David J. (2020) Distinct hypothalamic control of same- and opposite-sex mounting behaviour in mice. Nature . ISSN 0028-0836. (In Press) https://resolver.caltech.edu/CaltechAUTHORS:20200909-142458487

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Abstract

Animal behaviours that are superficially similar can express different intents in different contexts, but how this flexibility is achieved at the level of neural circuits is not understood. For example, males of many species can exhibit mounting behaviour towards same- or opposite-sex conspecifics, but it is unclear whether the intent and neural encoding of these behaviours are similar or different. Here we show that female- and male-directed mounting in male laboratory mice are distinguishable by the presence or absence of ultrasonic vocalizations (USVs), respectively. These and additional behavioural data suggest that most male-directed mounting is aggressive, although in rare cases it can be sexual. We investigated whether USV⁺ and USV⁻ mounting use the same or distinct hypothalamic neural substrates. Micro-endoscopic imaging of neurons positive for oestrogen receptor 1 (ESR1) in either the medial preoptic area (MPOA) or the ventromedial hypothalamus, ventrolateral subdivision (VMHvl) revealed distinct patterns of neuronal activity during USV⁺ and USV⁻ mounting, and the type of mounting could be decoded from population activity in either region. Intersectional optogenetic stimulation of MPOA neurons that express ESR1 and vesicular GABA transporter (VGAT) (MPOA^(ESR1∩VGAT) neurons) robustly promoted USV⁺ mounting, and converted male-directed attack to mounting with USVs. By contrast, stimulation of VMHvl neurons that express ESR1 (VMHvl^(ESR1) neurons) promoted USV⁻ mounting, and inhibited the USVs evoked by female urine. Terminal stimulation experiments suggest that these complementary inhibitory effects are mediated by reciprocal projections between the MPOA and VMHvl. Together, these data identify a hypothalamic subpopulation that is genetically enriched for neurons that causally induce a male reproductive behavioural state, and indicate that reproductive and aggressive states are represented by distinct population codes distributed between MPOA^(ESR1) and VMHvl^(ESR1) neurons, respectively. Thus, similar behaviours that express different internal states are encoded by distinct hypothalamic neuronal populations.


Item Type:Article
Related URLs:
URLURL TypeDescription
https://doi.org/10.1038/s41586-020-2995-0DOIArticle
https://rdcu.be/cbB63PublisherFree ReadCube access
https://doi.org/10.1038/s41586-020-03143-1DOIPublisher Correction
https://rdcu.be/cdakKPublisherFree ReadCube access - Publisher Correction
https://neuroethology.github.io/MARSRelated ItemCode
ORCID:
AuthorORCID
Kennedy, Ann0000-0002-3782-0518
Tai, Derek0000-0003-0609-5816
Anderson, David J.0000-0001-6175-3872
Alternate Title:Hypothalamic control of same- vs. opposite-sex mounting behavior in mice
Additional Information:© 2020 Nature Publishing Group. Received 17 December 2019; Accepted 22 September 2020; Published 02 December 2020. We thank X. Da, J. S. Chang and X. Wang for technical help; Y. Huang for genotyping; Caltech OLAR staff for animal care; J. Costanza for mouse colony management; Inscopix for technical support; C. Segalin and P. Perona for mouse tracking and behaviour classifier software; R. Axel and Y. Oka for constructive comments on the manuscript; C. Chiu for laboratory management; G. Mancuso for administrative assistance; and members of the Anderson laboratory for helpful comments on this project. The illustrations of mice are from TogoTV Picture Gallery (copyright 2016 DBCLS TogoTV). D.J.A. is an investigator of the Howard Hughes Medical Institute. This work was supported by NIH grants R01 MH085082 and R01 MH070053, and a grant from the Simons Collaboration on the Global Brain Foundation (award no. 542947) to D.J.A. T.K. is a recipient of HFSP Long-Term Fellowship. A.K. is a recipient of Helen Hay Whitney Foundation Postdoctoral Fellowship and NIMH K99 Pathway to Independence Award. Data availability: The data that support the finding of this study are available from the corresponding author upon request. Code availability: The custom codes used for pose tracking and behaviour annotation of the mice5 can be found at GitHub (https://neuroethology.github.io/MARS/). The other code that supports the finding of this study are available from the corresponding author upon request. Author Contributions: T.K. and D.J.A conceived and designed the study. T.K. performed and analysed fibre photometry experiments. T.K. and B.Y. performed and analysed micro-endoscope experiments. T.K., M.L. and D.T. performed and analysed optogenetic experiments. T.K. and D.T. performed and analysed chemogenetic experiments and other behaviour experiments. A.K. performed decoder analyses on mouse pose data and micro-endoscope data. I.A.W. wrote the code for the USV detection classifier. T.K. and A.K. prepared figures. T.K. and D.J.A. wrote the paper. The authors declare no competing interests. Peer review information: Nature thanks the anonymous reviewers for their contribution to the peer review of this work.
Errata:Karigo, T., Kennedy, A., Yang, B. et al. Publisher Correction: Distinct hypothalamic control of same- and opposite-sex mounting behaviour in mice. Nature (2021). https://doi.org/10.1038/s41586-020-03143-1
Group:Tianqiao and Chrissy Chen Institute for Neuroscience
Funders:
Funding AgencyGrant Number
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
NIHR01 MH085082
NIHR01 MH070053
Simons Foundation542947
Human Frontier Science ProgramUNSPECIFIED
Helen Hay Whitney FoundationUNSPECIFIED
Subject Keywords:Aggression; Neural circuits; Sexual behaviour; Social behaviour
Record Number:CaltechAUTHORS:20200909-142458487
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200909-142458487
Official Citation:Karigo, T., Kennedy, A., Yang, B. et al. Distinct hypothalamic control of same- and opposite-sex mounting behaviour in mice. Nature (2020). https://doi.org/10.1038/s41586-020-2995-0
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:105299
Collection:CaltechAUTHORS
Deposited By: George Porter
Deposited On:02 Dec 2020 20:02
Last Modified:06 Jan 2021 21:10

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