Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Enhanced partner preference in a promiscuous species by manipulating the expression of a single gene

Nature volume 429, pages 754–757 (2004)Cite this article

Abstract

The molecular mechanisms underlying the evolution of complex behaviour are poorly understood. The mammalian genus Microtus provides an excellent model for investigating the evolution of social behaviour. Prairie voles (Microtus ochrogaster) exhibit a monogamous social structure in nature, whereas closely related meadow voles (Microtus pennsylvanicus) are solitary and polygamous1. In male prairie voles, both vasopressin and dopamine act in the ventral forebrain to regulate selective affiliation between adult mates, known as pair bond formation, as assessed by partner preference in the laboratory2,3,4. The vasopressin V1a receptor (V1aR) is expressed at higher levels in the ventral forebrain of monogamous than in promiscuous vole species5, whereas dopamine receptor distribution is relatively conserved between species. Here we substantially increase partner preference formation in the socially promiscuous meadow vole by using viral vector V1aR gene transfer into the ventral forebrain. We show that a change in the expression of a single gene in the larger context of pre-existing genetic and neural circuits can profoundly alter social behaviour, providing a potential molecular mechanism for the rapid evolution of complex social behaviour.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Comparison of brain neurochemistry and behaviour in prairie and meadow voles.
Figure 2: V1aR autoradiography at the level of the ventral pallidum.
Figure 3: Partner preference test.
Figure 4: Partner preference test after eticlopride pretreatment.

Similar content being viewed by others

References

  1. Gruder-Adams, S. & Getz, L. L. Comparison of the mating system and paternal behavior in Microtus ochragaster and M. pennsylvanicus. J. Mamm. 66, 165–167 (1985)

    Article  Google Scholar 

  2. Aragona, B. J., Liu, Y., Curtis, J. T., Stephan, F. K. & Wang, Z. A critical role for nucleus accumbens dopamine in partner-preference formation in male prairie voles. J. Neurosci. 23, 3483–3490 (2003)

    Article  CAS  Google Scholar 

  3. Gingrich, B., Liu, Y., Cascio, C., Wang, Z. & Insel, T. R. Dopamine D2 receptors in the nucleus accumbens are important for social attachment in female prairie voles (Microtus ochrogaster). Behav. Neurosci. 114, 173–183 (2000)

    Article  CAS  Google Scholar 

  4. Lim, M. M. & Young, L. J. Vasopressin-dependent neural circuits underlying pair bonding in the monogamous prairie vole. Neuroscience 125, 35–45 (2004)

    Article  CAS  Google Scholar 

  5. Insel, T. R., Wang, Z. X. & Ferris, C. F. Patterns of brain vasopressin receptor distribution associated with social organization in microtine rodents. J. Neurosci. 14, 5381–5392 (1994)

    Article  CAS  Google Scholar 

  6. Kleiman, D. G. Monogamy in mammals. Q. Rev. Biol. 52, 39–69 (1977)

    Article  CAS  Google Scholar 

  7. Winslow, J. T., Hastings, N., Carter, C. S., Harbaugh, C. R. & Insel, T. R. A role for central vasopressin in pair bonding in monogamous prairie voles. Nature 365, 545–548 (1993)

    Article  ADS  CAS  Google Scholar 

  8. Wang, Z., Ferris, C. F. & De Vries, G. J. Role of septal vasopressin innervation in paternal behavior in prairie voles (Microtus ochrogaster). Proc. Natl Acad. Sci. USA 91, 400–404 (1994)

    Article  ADS  CAS  Google Scholar 

  9. Young, L. J., Nilsen, R., Waymire, K. G., MacGregor, G. R. & Insel, T. R. Increased affiliative response to vasopressin in mice expressing the V1a receptor from a monogamous vole. Nature 400, 766–768 (1999)

    Article  ADS  CAS  Google Scholar 

  10. Lim, M. M., Murphy, A. Z. & Young, L. J. Ventral striatopallidal oxytocin and vasopressin V1a receptors in the monogamous prairie vole (Microtus ochrogaster). J. Comp. Neurol. 468, 555–570 (2004)

    Article  CAS  Google Scholar 

  11. Young, L. J., Toloczko, D. & Insel, T. R. Localization of vasopressin (V1a) receptor binding and mRNA in the rhesus monkey brain. J. Neuroendocrinol. 11, 291–297 (1999)

    Article  CAS  Google Scholar 

  12. Young, L. J. Frank A. Beach Award. Oxytocin and vasopressin receptors and species-typical social behaviors. Horm. Behav. 36, 212–221 (1999)

    Article  CAS  Google Scholar 

  13. Wang, Z. et al. Vasopressin in the forebrain of common marmosets (Callithrix jacchus): studies with in situ hybridization, immunocytochemistry and receptor autoradiography. Brain Res. 768, 147–156 (1997)

    Article  ADS  CAS  Google Scholar 

  14. Bester-Meredith, J. K., Young, L. J. & Marler, C. A. Species differences in paternal behavior and aggression in peromyscus and their associations with vasopressin immunoreactivity and receptors. Horm. Behav. 36, 25–38 (1999)

    Article  CAS  Google Scholar 

  15. Parker, K. J. & Lee, T. M. Development of selective partner preferences in captive male and female meadow voles, Microtus pennsylvanicus. Anim. Behav. 61, 1217–1226 (2001)

    Article  Google Scholar 

  16. Wang, Z. et al. Dopamine D2 receptor-mediated regulation of partner preferences in female prairie voles (Microtus ochrogaster): a mechanism for pair bonding? Behav. Neurosci. 113, 602–611 (1999)

    Article  CAS  Google Scholar 

  17. Roberts, R. L., Williams, J. R., Wang, A. K. & Carter, C. S. Cooperative breeding and monogamy in prairie voles: influence of the sire and geographical variation. Anim. Behav. 55, 1131–1140 (1998)

    Article  CAS  Google Scholar 

  18. Bielsky, I. F., Bao-Hu, S., Szegda, K. L., Westphal, H. & Young, L. J. Profound impairment in social recognition and reduction in anxiety-like behavior in vasopressin V1a receptor knockout mice. Neuropsychopharmacology 29, 483–493 (2004)

    Article  CAS  Google Scholar 

  19. Landgraf, R. et al. Viral vector-mediated gene transfer of the vole V1a vasopressin receptor in the rat septum: improved social discrimination and active social behaviour. Eur. J. Neurosci. 18, 403–411 (2003)

    Article  Google Scholar 

  20. Aragona, B. J. et al. Opposite modulation of social attachment by D1- and D2-type dopamine receptor activation in nucleus accumbens shell. Horm. Behav. 44, 37 (2003)

    Google Scholar 

  21. Robinson, G. E. & Ben-Shahar, Y. Social behavior and comparative genomics: new genes or new gene regulation? Genes Brain Behav. 1, 197–203 (2002)

    Article  CAS  Google Scholar 

  22. Hammock, E. A. D. & Young, L. J. Functional microsatellite polymorphism associated with divergent social structure in vole species. Mol. Biol. Evol. (in the press)

  23. Phelps, S. M. & Young, L. J. Extraordinary diversity in vasopressin (V1a) receptor distributions among wild prairie voles (Microtus ochrogaster): patterns of variation and covariation. J. Comp. Neurol. 466, 564–576 (2003)

    Article  CAS  Google Scholar 

  24. Hammock, E. A. D. & Young, L. J. Variation in the vasopressin V1a receptor promoter and expression: implications for inter- and intraspecific variation in social behaviour. Eur. J. Neurosci. 16, 399–402 (2002)

    Article  Google Scholar 

  25. Barberis, C. & Tribollet, E. Vasopressin and oxytocin receptors in the central nervous system. Crit. Rev. Neurobiol. 10, 119–154 (1996)

    Article  CAS  Google Scholar 

  26. Kim, S. J. et al. Transmission disequilibrium testing of arginine vasopressin receptor 1A (AVPR1A) polymorphisms in autism. Mol. Psychiatry 7, 503–507 (2002)

    Article  CAS  Google Scholar 

  27. Pitkow, L. J. et al. Facilitation of affiliation and pair-bond formation by vasopressin receptor gene transfer into the ventral forebrain of a monogamous vole. J. Neurosci. 21, 7392–7396 (2001)

    Article  CAS  Google Scholar 

  28. Young, L. J., Winslow, J. T., Nilsen, R. & Insel, T. R. Species differences in V1a receptor gene expression in monogamous and nonmonogamous voles: behavioral consequences. Behav. Neurosci. 111, 599–605 (1997)

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank C. A. Sharer for contributing to the initial viral vector work, L. Miller for assistance with meadow vole breeding, and A. Z. Murphy and E. A. D. Hammock for their critical readings of the manuscript. Funding for this work was provided by grants from the NIH to M.M.L., Z.X.W., L.J.Y. and the Yerkes Center, and by a NSF STC grant to the Center for Behavioral Neuroscience.Authors' contributions M.M.L. performed the experiments and wrote the manuscript. Z.X.W. provided the animals and behavioural testing equipment for the pilot studies, the D2 autoradiography protocol and scientific input. D.E.O. assisted with the paternal behaviour testing. X.H.R. and E.F.T. generated the viral vectors. L.J.Y. conceived the idea and co-wrote the manuscript.

Author information

Authors and Affiliations

  1. Center for Behavioral Neuroscience and Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, Georgia, 30322, USA

    Miranda M. Lim, Daniel E. Olazábal & Larry J. Young

  2. Department of Psychology and Neuroscience Program, Florida State University, Tallahassee, Florida, 32306, USA

    Zuoxin Wang

  3. Harvard Institutes of Medicine and Beth Israel Deaconess Medical Center, Boston, Massachusetts, 02115, USA

    Xianghui Ren & Ernest F. Terwilliger

Authors
  1. Miranda M. Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Zuoxin Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daniel E. Olazábal
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Xianghui Ren
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ernest F. Terwilliger
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Larry J. Young
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Larry J. Young.

Ethics declarations

Competing interests

The authors declare that they have no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lim, M., Wang, Z., Olazábal, D. et al. Enhanced partner preference in a promiscuous species by manipulating the expression of a single gene. Nature 429, 754–757 (2004). https://doi.org/10.1038/nature02539

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature02539

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing