Loss of oxytocin receptor function disrupts neural signatures of pair bonding and fidelity in the nucleus accumbens

Enduring relationships dramatically shape behaviors by promoting affiliation between familiar individuals; however, the neural mechanisms driving attachments remain unclear. Oxytocin receptor (Oxtr) signaling in the nucleus accumbens (NAc) reinforces pair bond formation in socially monogamous prairie voles. How Oxtr influences NAc activity during affiliative behaviors with partners and rejection of strangers is unknown.

Using in vivo fiber photometry, we demonstrate that genetic loss of Oxtr sex-specifically disrupts attachment behaviors and associated NAc activity. In females, loss of Oxtr reduces prosocial behaviors and NAc activity during initial chemosensory investigation of novel males; however, partner-directed affiliative behavior and associated activity increase independently of Oxtr. In males, loss of Oxtr increases prosocial investigation of novel females, and initial behavioral and neural activity patterns predict future partner preference in Oxtr-null males.

These findings reveal sex-specific roles for Oxtr in early pair bond development through modulation of prosociality and sensory processing. We would like to thank Charles Frye for assistance with statistics. We also thank Kevin Bender and the members of the Manoli Lab for thoughtful comments on the manuscript.

K.L.P.L. discloses support for the research of this work from the National Institute of Health BRAIN Initiative [grant number 1K99MH135061-01]. D.S.M. discloses support for publication of this work from the National Institutes of Health [grant number R01MH123513], National Science Foundation [grant number 1556974], Burroughs Wellcome Fund [grant number 1015667], and Whitehall Foundation [grant number 2018-08-83]. All other authors declare no relevant funding.

Department of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, CA, USA Kimberly L. See, Michael Sherman & Devanand S. Manoli Center for Integrative Neuroscience, University of California, San Francisco, San Francisco, CA, USA Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, CA, USA Neurosciences Graduate Program, University of California, San Francisco, San Francisco, CA, USA Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA The authors declare no competing interests.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material.