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A Neuro-hormonal Circuit for Paternal Behavior Controlled by a Hypothalamic Network Oscillation

Stagkourakis, Stefanos and Smiley, Kristina O. and Williams, Paul and Kakadellis, Sarah and Ziegler, Katharina and Bakker, Joanne and Brown, Rosemary S. E. and Harkany, Tibor and Grattan, David R. and Broberger, Christian (2020) A Neuro-hormonal Circuit for Paternal Behavior Controlled by a Hypothalamic Network Oscillation. Cell, 182 (4). pp. 960-975. ISSN 0092-8674.

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Parental behavior is pervasive throughout the animal kingdom and essential for species survival. However, the relative contribution of the father to offspring care differs markedly across animals, even between related species. The mechanisms that organize and control paternal behavior remain poorly understood. Using Sprague-Dawley rats and C57BL/6 mice, two species at opposite ends of the paternal spectrum, we identified that distinct electrical oscillation patterns in neuroendocrine dopamine neurons link to a chain of low dopamine release, high circulating prolactin, prolactin receptor-dependent activation of medial preoptic area galanin neurons, and paternal care behavior in male mice. In rats, the same parameters exhibit inverse profiles. Optogenetic manipulation of these rhythms in mice dramatically shifted serum prolactin and paternal behavior, whereas injecting prolactin into non-paternal rat sires triggered expression of parental care. These findings identify a frequency-tuned brain-endocrine-brain circuit that can act as a gain control system determining a species’ parental strategy.

Item Type:Article
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Stagkourakis, Stefanos0000-0003-1218-791X
Broberger, Christian0000-0002-7050-8809
Additional Information:© 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license ( Received 29 October 2018, Revised 21 October 2019, Accepted 9 July 2020, Available online 6 August 2020. The authors thank Dr. G. Spigolon for advice regarding experiments and Dr. K. Ampatzis for advice regarding illustrations. Members of the Broberger laboratory are thanked for discussions during preparation of this manuscript and Drs. N.G. Larsson and O. Kiehn for sharing the DAT-Cre and floxed-tdTomato mice, respectively. This study was supported by grants from the European Research Council (261286-ENDOSWITCH to C.B. and ERC-AdG-2015-695136 to T.H.); the Swedish Research Council (2018-02480), Strategic Research Program in Diabetes at Karolinska Institutet and StratNeuro, Hjärnfonden (Swedish Brain Foundation), Novo Nordisk Fonden, and internal funds from Karolinska Institutet (to C.B.), and EMBO ALTF 736-2018 (to S.S.). Author Contributions: S.S., P.W., S.K., and K.Z. designed, performed, and analyzed experiments. K.O.S., R.S.E.B., and D.R.G. collaborated on data involving the prolactin receptor floxed mouse. J.B. and T.H. collaborated on data involving the Gal-Cre mice. C.B. designed experiments. S.S. and C.B. wrote the manuscript. All authors reviewed the manuscript. The authors declare no competing interests.
Funding AgencyGrant Number
European Research Council (ERC)261286
European Research Council (ERC)695136
Karolinska InstitutetUNSPECIFIED
Swedish Brain FoundationUNSPECIFIED
Novo Nordisk FoundationUNSPECIFIED
European Molecular Biology Organization (EMBO)ALTF 736-2018
Subject Keywords:arcuate nucleus; dopamine; gap junction; medial preoptic area; neuronal network; oscillation; parental; paternal; prolactin; species difference
Issue or Number:4
Record Number:CaltechAUTHORS:20200818-151256129
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Official Citation:Stefanos Stagkourakis, Kristina O. Smiley, Paul Williams, Sarah Kakadellis, Katharina Ziegler, Joanne Bakker, Rosemary S.E. Brown, Tibor Harkany, David R. Grattan, Christian Broberger, A Neuro-hormonal Circuit for Paternal Behavior Controlled by a Hypothalamic Network Oscillation, Cell, Volume 182, Issue 4, 2020, Pages 960-975.e15, ISSN 0092-8674, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:105015
Deposited By: George Porter
Deposited On:18 Aug 2020 22:38
Last Modified:27 Aug 2020 18:10

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