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.

The neural mechanisms and circuitry of the pair bond

Abstract

Love is one of our most powerful emotions, inspiring some of the greatest art, literature and conquests of human history. Although aspects of love are surely unique to our species, human romantic relationships are displays of a mating system characterized by pair bonding, likely built on ancient foundational neural mechanisms governing individual recognition, social reward, territorial behaviour and maternal nurturing. Studies in monogamous prairie voles and mice have revealed precise neural mechanisms regulating processes essential for the pair bond. Here, we discuss current viewpoints on the biology underlying pair bond formation, its maintenance and associated behaviours from neural and evolutionary perspectives.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Fig. 1: Individual variation in oxytocin receptor expression in the nucleus accumbens confers resilience to neonatal neglect.
Fig. 2: A neural model of pair bond formation.
Fig. 3: Schematics illustrating selected processes proposed to be involved in pair bonding on the basis of our model.
Fig. 4: The corticotropin-releasing factor system and oxytocin interact to maintain the pair bond.

References

  1. 1.

    Raghanti, M. A. et al. A neurochemical hypothesis for the origin of hominids. Proc. Natl Acad. Sci. USA 115, E1108–E1116 (2018).

    CAS  PubMed  Google Scholar 

  2. 2.

    Young, L. J. Being human: love: neuroscience reveals all. Nature 457, 148 (2009).

    CAS  PubMed  Google Scholar 

  3. 3.

    Bull, C. M. Monogamy in lizards. Behav. Processes 51, 7–20 (2000).

    CAS  PubMed  Google Scholar 

  4. 4.

    Whiteman, E. A. & Cote, I. M. Monogamy in marine fishes. Biol. Rev. Camb. Philos. Soc. 79, 351–375 (2004).

    CAS  PubMed  Google Scholar 

  5. 5.

    Dunn, P. O., Whittingham, L. A. & Pitcher, T. E. Mating systems, sperm competition, and the evolution of sexual dimorphism in birds. Evolution 55, 161–175 (2001).

    CAS  PubMed  Google Scholar 

  6. 6.

    Lukas, D. & Clutton-Brock, T. H. The evolution of social monogamy in mammals. Science 341, 526–530 (2013).

    CAS  PubMed  Google Scholar 

  7. 7.

    House, J. S., Landis, K. R. & Umberson, D. Social relationships and health. Science 241, 540–545 (1988).

    CAS  PubMed  Google Scholar 

  8. 8.

    Bifulco, A., Moran, P. M., Ball, C. & Bernazzani, O. Adult attachment style. I: Its relationship to clinical depression. Soc. Psychiatry Psychiatr. Epidemiol. 37, 50–59 (2002).

    CAS  PubMed  Google Scholar 

  9. 9.

    Kiecolt-Glaser, J. K. et al. Hostile marital interactions, proinflammatory cytokine production, and wound healing. Arch. Gen. Psychiatry 62, 1377–1384 (2005).

    PubMed  Google Scholar 

  10. 10.

    Orth-Gomer, K. et al. Marital stress worsens prognosis in women with coronary heart disease: The Stockholm Female Coronary Risk Study. JAMA 284, 3008–3014 (2000).

    CAS  PubMed  Google Scholar 

  11. 11.

    Johnson, Z. V. & Young, L. J. Neurobiological mechanisms of social attachment and pair bonding. Curr. Opin. Behav. Sci. 3, 38–44 (2015).

    PubMed  PubMed Central  Google Scholar 

  12. 12.

    McGraw, L. A. & Young, L. J. The prairie vole: an emerging model organism for understanding the social brain. Trends Neurosci. 33, 103–109 (2010).

    CAS  PubMed  Google Scholar 

  13. 13.

    Ross, H. E. & Young, L. J. Oxytocin and the neural mechanisms regulating social cognition and affiliative behavior. Front. Neuroendocrinol. 30, 534–547 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Young, L. J. & Wang, Z. The neurobiology of pair bonding. Nat. Neurosci. 7, 1048–1054 (2004).

    CAS  PubMed  Google Scholar 

  15. 15.

    Young, K. A., Gobrogge, K. L., Liu, Y. & Wang, Z. The neurobiology of pair bonding: insights from a socially monogamous rodent. Front. Neuroendocrinol. 32, 53–69 (2011).

    PubMed  Google Scholar 

  16. 16.

    Ahern, T. H., Hammock, E. A. & Young, L. J. Parental division of labor, coordination, and the effects of family structure on parenting in monogamous prairie voles (Microtus ochrogaster). Dev. Psychobiol. 53, 118–131 (2011).

    PubMed  Google Scholar 

  17. 17.

    Williams, J. R., Insel, T. R., Harbaugh, C. R. & Carter, C. S. Oxytocin administered centrally facilitates formation of a partner preference in female prairie voles (Microtus ochrogaster). J. Neuroendocrinol. 6, 247–250 (1994).

    CAS  PubMed  Google Scholar 

  18. 18.

    Numan, M. & Young, L. J. Neural mechanisms of mother–infant bonding and pair bonding: similarities, differences, and broader implications. Horm. Behav. 77, 98–112 (2016).

    CAS  PubMed  Google Scholar 

  19. 19.

    Rilling, J. K. & Young, L. J. The biology of mammalian parenting and its effect on offspring social development. Science 345, 771–776 (2014).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. 20.

    Ferguson, J. N. et al. Social amnesia in mice lacking the oxytocin gene. Nat. Genet. 25, 284–288 (2000).

    CAS  PubMed  Google Scholar 

  21. 21.

    Burkett, J. P. et al. Oxytocin-dependent consolation behavior in rodents. Science 351, 375–378 (2016). This study demonstrates that consoling behaviour in prairie voles displays multiple qualities that are characteristic of empathy and is regulated by OT receptors in the anterior cingulate cortex.

    CAS  PubMed  PubMed Central  Google Scholar 

  22. 22.

    Nagasawa, M. et al. Social evolution. Oxytocin-gaze positive loop and the coevolution of human-dog bonds. Science 348, 333–336 (2015).

    CAS  PubMed  Google Scholar 

  23. 23.

    Burbach, P., Young, L. J. & Russell, J. in Knobil an Neill’s Physiology of Reproduction. (ed. Neill, J. D.) 3055–3127 (Elsevier, 2006).

  24. 24.

    Johnson, Z. V. & Young, L. J. Oxytocin and vasopressin neural networks: implications for social behavioral diversity and translational neuroscience. Neurosci. Biobehav. Rev. 76, 87–98 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 25.

    Knobloch, H. S. et al. Evoked axonal oxytocin release in the central amygdala attenuates fear response. Neuron 73, 553–566 (2012).

    CAS  PubMed  Google Scholar 

  26. 26.

    Ross, H. E. et al. Characterization of the oxytocin system regulating affiliative behavior in female prairie voles. Neuroscience 162, 892–903 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Dobolyi, A., Cservenak, M. & Young, L. J. Thalamic integration of social stimuli regulating parental behavior and the oxytocin system. Front. Neuroendocrinol. https://doi.org/S0091-3022(18)30050-5 (2018).

  28. 28.

    de Waal, F. B. M. & Preston, S. D. Mammalian empathy: behavioural manifestations and neural basis. Nat. Rev. Neurosci. 18, 498–509 (2017).

    PubMed  Google Scholar 

  29. 29.

    Cho, M. M., DeVries, A. C., Williams, J. R. & Carter, C. S. The effects of oxytocin and vasopressin on partner preferences in male and female prairie voles (Microtus ochrogaster). Behav. Neurosci. 113, 1071–1079 (1999).

    CAS  PubMed  Google Scholar 

  30. 30.

    Insel, T. R. & Hulihan, T. J. A gender-specific mechanism for pair bonding: oxytocin and partner preference formation in monogamous voles. Behav. Neurosci. 109, 782–789 (1995).

    CAS  PubMed  Google Scholar 

  31. 31.

    Johnson, Z. V. et al. Central oxytocin receptors mediate mating-induced partner preferences and enhance correlated activation across forebrain nuclei in male prairie voles. Horm. Behav. 79, 8–17 (2016). This paper demonstrates that OT signalling throughout the brain coordinates activity in many nodes of the pair-bonding network, supporting the view that OT facilitates the flow of information across the brain, acting as the ‘grease’ of the social brain.

    CAS  PubMed  Google Scholar 

  32. 32.

    Insel, T. R. & Shapiro, L. E. Oxytocin receptor distribution reflects social organization in monogamous and polygamous voles. Proc. Natl Acad. Sci. USA 89, 5981–5985 (1992).

    CAS  PubMed  Google Scholar 

  33. 33.

    Young, L. J., Lim, M. M., Gingrich, B. & Insel, T. R. Cellular mechanisms of social attachment. Horm. Behav. 40, 133–138 (2001).

    CAS  PubMed  Google Scholar 

  34. 34.

    Keebaugh, A. C., Barrett, C. E., Laprairie, J. L., Jenkins, J. J. & Young, L. J. RNAi knockdown of oxytocin receptor in the nucleus accumbens inhibits social attachment and parental care in monogamous female prairie voles. Soc. Neurosci. 10, 561–570 (2015).

    PubMed  PubMed Central  Google Scholar 

  35. 35.

    Keebaugh, A. C. & Young, L. J. Increasing oxytocin receptor expression in the nucleus accumbens of pre-pubertal female prairie voles enhances alloparental responsiveness and partner preference formation as adults. Horm. Behav. 60, 498–504 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. 36.

    King, L. B., Walum, H., Inoue, K., Eyrich, N. W. & Young, L. J. Variation in the oxytocin receptor gene predicts brain region-specific expression and social attachment. Biol. Psychiatry 80, 160–169 (2016). This paper demonstrates that the remarkable individual variation in OXTR expression in the striatum is largely determined by a set of SNPs in non-coding regions of the prairie vole Oxtr gene.

    CAS  PubMed  Google Scholar 

  37. 37.

    Olazabal, D. E. & Young, L. J. Oxytocin receptors in the nucleus accumbens facilitate “spontaneous” maternal behavior in adult female prairie voles. Neuroscience 141, 559–568 (2006).

    CAS  PubMed  Google Scholar 

  38. 38.

    Ophir, A. G., Gessel, A., Zheng, D. J. & Phelps, S. M. Oxytocin receptor density is associated with male mating tactics and social monogamy. Horm. Behav. 61, 445–453 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Barrett, C. E., Arambula, S. E. & Young, L. J. The oxytocin system promotes resilience to the effects of neonatal isolation on adult social attachment in female prairie voles. Transl Psychiatry 5, e606 (2015). This paper shows that daily neonatal social isolations disrupt adult pair bond formation and that those animals with many OXTRs in the NAc are resilient to the effects of this model of neglect.

    CAS  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Albers, H. E. The regulation of social recognition, social communication and aggression: vasopressin in the social behavior neural network. Horm. Behav. 61, 283–292 (2012).

    CAS  PubMed  Google Scholar 

  41. 41.

    Nair, H. P. & Young, L. J. Vasopressin and pair-bond formation: genes to brain to behavior. Physiology 21, 146–152 (2006).

    CAS  PubMed  Google Scholar 

  42. 42.

    Donaldson, Z. R., Spiegel, L. & Young, L. J. Central vasopressin V1a receptor activation is independently necessary for both partner preference formation and expression in socially monogamous male prairie voles. Behav. Neurosci. 124, 159–163 (2010).

    PubMed  PubMed Central  Google Scholar 

  43. 43.

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

    CAS  PubMed  Google Scholar 

  44. 44.

    Barrett, C. E. et al. Variation in vasopressin receptor (Avpr1a) expression creates diversity in behaviors related to monogamy in prairie voles. Horm. Behav. 63, 518–526 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  45. 45.

    Lim, M. M. et al. Enhanced partner preference in a promiscuous species by manipulating the expression of a single gene. Nature 429, 754–757 (2004). This paper demonstrates that species differences in vasopressin receptor expression in the VP mediate species differences in pair bonding by showing that overexpressing the prairie vole vasopressin receptor in the VP of meadow voles causes them to form partner preferences.

    CAS  PubMed  Google Scholar 

  46. 46.

    Liu, Y., Curtis, J. T. & Wang, Z. X. Vasopressin in the lateral septum regulates pair bond formation in male prairie voles (Microtus ochrogaster). Behav. Neurosci. 115, 910–919 (2001).

    CAS  PubMed  Google Scholar 

  47. 47.

    Everts, H. G. & Koolhaas, J. M. Lateral septal vasopressin in rats: role in social and object recognition? Brain Res. 760, 1–7 (1997).

    CAS  PubMed  Google Scholar 

  48. 48.

    Bielsky, I. F., Hu, S. B., Ren, X., Terwilliger, E. F. & Young, L. J. The V1a vasopressin receptor is necessary and sufficient for normal social recognition: a gene replacement study. Neuron 47, 503–513 (2005).

    CAS  PubMed  Google Scholar 

  49. 49.

    Tobin, V. A. et al. An intrinsic vasopressin system in the olfactory bulb is involved in social recognition. Nature 464, 413–417 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. 50.

    Gobrogge, K. L., Liu, Y., Young, L. J. & Wang, Z. Anterior hypothalamic vasopressin regulates pair-bonding and drug-induced aggression in a monogamous rodent. Proc. Natl Acad. Sci. USA 106, 19144–19149 (2009).

    CAS  PubMed  Google Scholar 

  51. 51.

    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).

    CAS  PubMed  Google Scholar 

  52. 52.

    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).

    CAS  PubMed  Google Scholar 

  53. 53.

    Young, L. & Alexander, B. The Chemistry Between Us: Love, Sex, and the Science of Attraction. (Current, 2012).

  54. 54.

    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).

    CAS  PubMed  Google Scholar 

  55. 55.

    Hammock, E. A. & Young, L. J. Microsatellite instability generates diversity in brain and sociobehavioral traits. Science 308, 1630–1634 (2005).

    CAS  PubMed  Google Scholar 

  56. 56.

    Okhovat, M., Berrio, A., Wallace, G., Ophir, A. G. & Phelps, S. M. Sexual fidelity trade-offs promote regulatory variation in the prairie vole brain. Science 350, 1371–1374 (2015). This study demonstrates that sequence variation in the vasopressin receptor gene influences expression in a brain region involved in spatial memory and influences sexual fidelity in a naturalistic setting.

    CAS  PubMed  Google Scholar 

  57. 57.

    Ophir, A. G. Navigating monogamy: nonapeptide sensitivity in a memory neural circuit may shape social behavior and mating decisions. Front. Neurosci. 11, 397 (2017).

    PubMed  PubMed Central  Google Scholar 

  58. 58.

    Aragona, B. J. et al. Nucleus accumbens dopamine differentially mediates the formation and maintenance of monogamous pair bonds. Nat. Neurosci. 9, 133–139 (2006). This paper demonstrates that the emergence of selective aggression following pair bonding is mediated by a change in the ratio of D1Rs to D2Rs in the NAc.

    CAS  PubMed  Google Scholar 

  59. 59.

    Resendez, S. L., Kuhnmuench, M., Krzywosinski, T. & Aragona, B. J. kappa-Opioid receptors within the nucleus accumbens shell mediate pair bond maintenance. J. Neurosci. 32, 6771–6784 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. 60.

    Resendez, S. L. et al. Dopamine and opioid systems interact within the nucleus accumbens to maintain monogamous pair bonds. eLife 5, e15325 (2016).

    PubMed  PubMed Central  Google Scholar 

  61. 61.

    Burkett, J. P., Spiegel, L. L., Inoue, K., Murphy, A. Z. & Young, L. J. Activation of mu-opioid receptors in the dorsal striatum is necessary for adult social attachment in monogamous prairie voles. Neuropsychopharmacology 36, 2200–2210 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  62. 62.

    Resendez, S. L. et al. mu-Opioid receptors within subregions of the striatum mediate pair bond formation through parallel yet distinct reward mechanisms. J. Neurosci. 33, 9140–9149 (2013).

    CAS  PubMed  Google Scholar 

  63. 63.

    Burkett, J. P. & Young, L. J. The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction. Psychopharmacol. (Berl.) 224, 1–26 (2012).

    CAS  Google Scholar 

  64. 64.

    Di Chiara, G. et al. Dopamine and drug addiction: the nucleus accumbens shell connection. Neuropharmacology 47 (Suppl. 1), 227–241 (2004).

    PubMed  Google Scholar 

  65. 65.

    Volkow, N. D., Fowler, J. S., Wang, G. J., Baler, R. & Telang, F. Imaging dopamine’s role in drug abuse and addiction. Neuropharmacology 56 (Suppl. 1), 3–8 (2009).

    CAS  PubMed  Google Scholar 

  66. 66.

    Liu, Y. et al. Nucleus accumbens dopamine mediates amphetamine-induced impairment of social bonding in a monogamous rodent species. Proc. Natl Acad. Sci. USA 107, 1217–1222 (2010).

    CAS  PubMed  Google Scholar 

  67. 67.

    Liu, Y., Young, K. A., Curtis, J. T., Aragona, B. J. & Wang, Z. Social bonding decreases the rewarding properties of amphetamine through a dopamine D1 receptor-mediated mechanism. J. Neurosci. 31, 7960–7966 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  68. 68.

    Burkett, J. & Young, L. Love and addiction: an uneasy marriage? A response to “The devil is in the differences”. Psychopharmacology 224, 31–32 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  69. 69.

    Hostetler, C. M. & Ryabinin, A. E. Love and addiction: the devil is in the differences: a commentary on “the behavioral, anatomical and pharmacological parallels between social attachment, love and addiction”. Psychopharmacology 224, 27–29; discussion 31–32 (2012).

    CAS  PubMed  Google Scholar 

  70. 70.

    Dolen, G., Darvishzadeh, A., Huang, K. W. & Malenka, R. C. Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin. Nature 501, 179–184 (2013).

    PubMed  PubMed Central  Google Scholar 

  71. 71.

    Larke, R. H., Maninger, N., Ragen, B. J., Mendoza, S. P. & Bales, K. L. Serotonin 1A agonism decreases affiliative behavior in pair-bonded titi monkeys. Horm. Behav. 86, 71–77 (2016).

    CAS  PubMed  PubMed Central  Google Scholar 

  72. 72.

    Lim, M. M. et al. CRF receptors in the nucleus accumbens modulate partner preference in prairie voles. Horm. Behav. 51, 508–515 (2007).

    CAS  PubMed  PubMed Central  Google Scholar 

  73. 73.

    DeVries, A. C., DeVries, M. B., Taymans, S. & Carter, C. S. Modulation of pair bonding in female prairie voles (Microtus ochrogaster) by corticosterone. Proc. Natl Acad. Sci. USA 92, 7744–7748 (1995).

    CAS  PubMed  Google Scholar 

  74. 74.

    DeVries, A. C., DeVries, M. B., Taymans, S. E. & Carter, C. S. Stress has sexually dimorphic effects on pair bonding in prairie voles. Proc. Natl Acad. Sci. USA 93, 11980–11984 (1996).

    CAS  PubMed  Google Scholar 

  75. 75.

    Johnson, Z. V., Walum, H., Xiao, Y., Riefkohl, P. C. & Young, L. J. Oxytocin receptors modulate a social salience neural network in male prairie voles. Horm. Behav. 87, 16–24 (2017).

    CAS  PubMed  Google Scholar 

  76. 76.

    Brennan, P. A. & Kendrick, K. M. Mammalian social odours: attraction and individual recognition. Phil. Trans. R. Soc. B 361, 2061–2078 (2006).

    CAS  PubMed  Google Scholar 

  77. 77.

    Sanchez-Andrade, G. & Kendrick, K. M. The main olfactory system and social learning in mammals. Behav. Brain Res. 200, 323–335 (2009).

    PubMed  Google Scholar 

  78. 78.

    Oettl, L. L. et al. Oxytocin enhances social recognition by modulating cortical control of early olfactory processing. Neuron 90, 609–621 (2016). This study shows that in mice, OT acting in the cortical AON increases the excitatory drive of inhibitory neurons in the olfactory bulb to effectively increase the signal-to-noise ratio of olfactory output, thereby facilitating individual discrimination.

    CAS  PubMed  PubMed Central  Google Scholar 

  79. 79.

    Balu, R., Pressler, R. T. & Strowbridge, B. W. Multiple modes of synaptic excitation of olfactory bulb granule cells. J. Neurosci. 27, 5621–5632 (2007).

    CAS  PubMed  Google Scholar 

  80. 80.

    Insel, T., L. J., Y., Witt, D. & Crews, D. Gonadal steroids have paradoxical effects on brain oxytocin receptors. J. Neuroendo 5, 619–628 (1993).

    CAS  Google Scholar 

  81. 81.

    Tribollet, E., Barberis, C., Jard, S., Dubois-Dauphin, M. & Dreifuss, J. J. Localization and pharmacological characterization of high affinity binding sites for vasopressin and oxytocin in the rat brain by light microscopic autoradiography. Brain Res. 442, 105–118 (1988).

    CAS  PubMed  Google Scholar 

  82. 82.

    Witt, D. M., Carter, C. S. & Lnsel, T. R. Oxytocin receptor binding in female prairie voles: endogenous and exogenous oestradiol stimulation. J. Neuroendocrinol. 3, 155–161 (1991).

    CAS  PubMed  Google Scholar 

  83. 83.

    Marlin, B. J. et al. Oxytocin enables maternal behaviour by balancing cortical inhibition. Nature 520, 499–504 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  84. 84.

    Janak, P. H. & Tye, K. M. From circuits to behaviour in the amygdala. Nature 517, 284–292 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  85. 85.

    Beyeler, A. et al. Organization of valence-encoding and projection-defined neurons in the basolateral amygdala. Cell Rep. 22, 905–918 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  86. 86.

    Bielsky, I. F. & Young, L. J. Oxytocin, vasopressin, and social recognition in mammals. Peptides 25, 1565–1574 (2004).

    CAS  PubMed  Google Scholar 

  87. 87.

    Pro-Sistiaga, P. et al. Convergence of olfactory and vomeronasal projections in the rat basal telencephalon. J. Comp. Neurol. 504, 346–362 (2007).

    PubMed  Google Scholar 

  88. 88.

    Ferguson, J. N., Aldag, J. M., Insel, T. R. & Young, L. J. Oxytocin in the medial amygdala is essential for social recognition in the mouse. J. Neurosci. 21, 8278–8285 (2001).

    CAS  PubMed  Google Scholar 

  89. 89.

    Cushing, B. S., Mogekwu, N., Le, W. W., Hoffman, G. E. & Carter, C. S. Cohabitation induced Fos immunoreactivity in the monogamous prairie vole. Brain Res. 965, 203–211 (2003).

    CAS  PubMed  Google Scholar 

  90. 90.

    Northcutt, K. V. & Lonstein, J. S. Social contact elicits immediate-early gene expression in dopaminergic cells of the male prairie vole extended olfactory amygdala. Neuroscience 163, 9–22 (2009).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. 91.

    Kirkpatrick, B., Carter, C. S., Newman, S. W. & Insel, T. R. Axon-sparing lesions of the medial nucleus of the amygdala decrease affiliative behaviors in the prairie vole (Microtus ochrogaster): behavioral and anatomical specificity. Behav. Neurosci. 108, 501–513 (1994).

    CAS  PubMed  Google Scholar 

  92. 92.

    Gur, R., Tendler, A. & Wagner, S. Long-term social recognition memory is mediated by oxytocin-dependent synaptic plasticity in the medial amygdala. Biol. Psychiatry 76, 377–386 (2014).

    CAS  PubMed  Google Scholar 

  93. 93.

    Fang, L. Y., Quan, R. D. & Kaba, H. Oxytocin facilitates the induction of long-term potentiation in the accessory olfactory bulb. Neurosci. Lett. 438, 133–137 (2008).

    CAS  PubMed  Google Scholar 

  94. 94.

    Lin, Y. T., Huang, C. C. & Hsu, K. S. Oxytocin promotes long-term potentiation by enhancing epidermal growth factor receptor-mediated local translation of protein kinase Mzeta. J. Neurosci. 32, 15476–15488 (2012).

    CAS  PubMed  PubMed Central  Google Scholar 

  95. 95.

    Tomizawa, K. et al. Oxytocin improves long-lasting spatial memory during motherhood through MAP kinase cascade. Nat. Neurosci. 6, 384–390 (2003).

    CAS  PubMed  Google Scholar 

  96. 96.

    Vertes, R. P. Interactions among the medial prefrontal cortex, hippocampus and midline thalamus in emotional and cognitive processing in the rat. Neuroscience 142, 1–20 (2006).

    CAS  PubMed  Google Scholar 

  97. 97.

    Freeman, S. M. & Young, L. J. Comparative perspectives on oxytocin and vasopressin receptor research in rodents and primates: translational implications. J. Neuroendocrinol. https://doi.org/10.1111/jne.12382 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  98. 98.

    Raam, T., McAvoy, K. M., Besnard, A., Veenema, A. H. & Sahay, A. Hippocampal oxytocin receptors are necessary for discrimination of social stimuli. Nat. Commun. 8, 2001 (2017).

    PubMed  PubMed Central  Google Scholar 

  99. 99.

    Lin, Y. T. et al. Conditional deletion of hippocampal CA2/CA3a oxytocin receptors impairs the persistence of long-term social recognition memory in mice. J. Neurosci. 38, 1218–1231 (2018).

    CAS  PubMed  PubMed Central  Google Scholar 

  100. 100.

    Owen, S. F. et al. Oxytocin enhances hippocampal spike transmission by modulating fast-spiking interneurons. Nature 500, 458–462 (2013).

    CAS  PubMed  PubMed Central  Google Scholar 

  101. 101.

    Okuyama, T., Kitamura, T., Roy, D. S., Itohara, S. & Tonegawa, S. Ventral CA1 neurons store social memory. Science 353, 1536–1541 (2016). This study demonstrates the existence of a social engram, or a collection of neurons whose firing represents the identity of another individual, in the ventral hippocampus that projects to the NAc.

    CAS  PubMed  PubMed Central  Google Scholar 

  102. 102.

    Tonegawa, S., Liu, X., Ramirez, S. & Redondo, R. Memory engram cells have come of age. Neuron 87, 918–931 (2015).

    CAS  PubMed  Google Scholar 

  103. 103.

    Hung, L. W. et al. Gating of social reward by oxytocin in the ventral tegmental area. Science 357, 1406–1411 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  104. 104.

    Love, T. M. Oxytocin, motivation and the role of dopamine. Pharmacol. Biochem. Behav. 119, 49–60 (2014).

    CAS  PubMed  Google Scholar 

  105. 105.

    Williams, J., Catania, K. & Carter, C. Development of partner preferences in female prairie voles (Microtus ochrogaster): the role of social and sexual experience. Horm. Beh. 26, 339–349 (1992).

    CAS  Google Scholar 

  106. 106.

    Liu, Y. & Wang, Z. X. Nucleus accumbens oxytocin and dopamine interact to regulate pair bond formation in female prairie voles. Neuroscience 121, 537–544 (2003).

    CAS  PubMed  Google Scholar 

  107. 107.

    Romero-Fernandez, W., Borroto-Escuela, D. O., Agnati, L. F. & Fuxe, K. Evidence for the existence of dopamine D2-oxytocin receptor heteromers in the ventral and dorsal striatum with facilitatory receptor-receptor interactions. Mol. Psychiatry 18, 849–850 (2013).

    CAS  PubMed  Google Scholar 

  108. 108.

    Humphries, M. D. & Prescott, T. J. The ventral basal ganglia, a selection mechanism at the crossroads of space, strategy, and reward. Prog. Neurobiol. 90, 385–417 (2010).

    PubMed  Google Scholar 

  109. 109.

    Walum, H., Waldman, I. D. & Young, L. J. Statistical and methodological considerations for the interpretation of intranasal oxytocin studies. Biol. Psychiatry 79, 251–257 (2016).

    CAS  PubMed  Google Scholar 

  110. 110.

    Scheele, D. et al. Oxytocin enhances brain reward system responses in men viewing the face of their female partner. Proc. Natl Acad. Sci. USA 110, 20308–20313 (2013).

    CAS  PubMed  Google Scholar 

  111. 111.

    Bethlehem, R. A. I. et al. Intranasal oxytocin enhances intrinsic corticostriatal functional connectivity in women. Transl Psychiatry 7, e1099 (2017).

    CAS  PubMed  PubMed Central  Google Scholar 

  112. 112.

    Rogers, C. N. et al. Oxytocin- and arginine vasopressin-containing fibers in the cortex of humans, chimpanzees, and rhesus macaques. Am. J. Primatol. https://doi.org/10.1002/ajp.22875 (2018).

    Article  PubMed  PubMed Central  Google Scholar 

  113. 113.

    Amadei, E. A. et al. Dynamic corticostriatal activity biases social bonding in monogamous female prairie voles. Nature 546, 297–301 (2017). This study demonstrates that modulation of NAc gamma oscillations by mPFC theta oscillations predicts the onset of affiliative huddling after mating and causally facilitates partner preference formation.

    CAS  PubMed  PubMed Central  Google Scholar 

  114. 114.

    Smith, K. S., Tindell, A. J., Aldridge, J. W. & Berridge, K. C. Ventral pallidum roles in reward and motivation. Behav. Brain Res. 196, 155–167 (2009).

    PubMed  Google Scholar 

  115. 115.

    Bosch, O. J., Nair, H. P., Ahern, T. H., Neumann, I. D. & Young, L. J. The CRF system mediates increased passive stress-coping behavior following the loss of a bonded partner in a monogamous rodent. Neuropsychopharmacology 34, 1406–1415 (2009).

    CAS  PubMed  Google Scholar 

  116. 116.

    Pohl, T. T., Young, L. J. & Bosch, O. J. Lost connections: oxytocin and the neural, physiological, and behavioral consequences of disrupted relationships. Int. J. Psychophysiol. https://doi.org/S0167-8760(17)30446-4 (2018).

  117. 117.

    Bosch, O. J., Pohl, T. T., Neumann, I. D. & Young, L. J. Abandoned prairie vole mothers show normal maternal care but altered emotionality: Potential influence of the brain corticotropin-releasing factor system. Behav. Brain Res. 341, 114–121 (2018).

    CAS  PubMed  Google Scholar 

  118. 118.

    Osako, Y. et al. Partner loss in monogamous rodents: modulation of pain and emotional behavior in male prairie voles. Psychosom. Med. 80, 62–68 (2018).

    PubMed  PubMed Central  Google Scholar 

  119. 119.

    Dabrowska, J. et al. Neuroanatomical evidence for reciprocal regulation of the corticotrophin-releasing factor and oxytocin systems in the hypothalamus and the bed nucleus of the stria terminalis of the rat: implications for balancing stress and affect. Psychoneuroendocrinology 36, 1312–1326 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  120. 120.

    Bosch, O. J. et al. Oxytocin in the nucleus accumbens shell reverses CRFR2-evoked passive stress-coping after partner loss in monogamous male prairie voles. Psychoneuroendocrinology 64, 66–78 (2016). This study suggests that the emergence of depressive-like behaviour following social loss is mediated by CRFR2 activation in the NAc, which then reduces OT signalling, thereby maintaining the pair bond by inducing an aversive state following separation from the partner.

    CAS  PubMed  Google Scholar 

  121. 121.

    Resendez, S. L. & Aragona, B. J. Aversive motivation and the maintenance of monogamous pair bonding. Rev. Neurosci. 24, 51–60 (2013).

    CAS  PubMed  Google Scholar 

  122. 122.

    Young, L. J. & Barrett, C. E. Neuroscience. Can oxytocin treat autism? Science 347, 825–826 (2015).

    CAS  PubMed  Google Scholar 

  123. 123.

    Modi, M. E. et al. Melanocortin receptor agonists facilitate oxytocin-dependent partner preference formation in the prairie vole. Neuropsychopharmacology 40, 1856–1865 (2015).

    CAS  PubMed  PubMed Central  Google Scholar 

  124. 124.

    Modi, M. E. & Young, L. J. D-cycloserine facilitates socially reinforced learning in an animal model relevant to autism spectrum disorders. Biol. Psychiatry 70, 298–304 (2011).

    CAS  PubMed  PubMed Central  Google Scholar 

  125. 125.

    Young, L. J., Pitkow, L. J. & Ferguson, J. N. Neuropeptides and social behavior: animal models relevant to autism. Mol. Psychiatry 7, S38–S39 (2002).

    PubMed  Google Scholar 

  126. 126.

    Belsky, J., Steinberg, L. & Draper, P. Childhood experience, interpersonal development, and reproductive strategy: and evolutionary theory of socialization. Child Dev. 62, 647–670 (1991).

    CAS  PubMed  Google Scholar 

  127. 127.

    Belsky, J. et al. Family rearing antecedents of pubertal timing. Child Dev. 78, 1302–1321 (2007).

    PubMed  Google Scholar 

  128. 128.

    Bogaert, A. F. Menarche and father absence in a national probability sample. J. Biosoc. Sci. 40, 623–636 (2008).

    PubMed  Google Scholar 

  129. 129.

    Ellis, B. J. & Essex, M. J. Family environments, adrenarche, and sexual maturation: a longitudinal test of a life history model. Child Dev. 78, 1799–1817 (2007).

    PubMed  Google Scholar 

  130. 130.

    Pesonen, A. K. et al. Reproductive traits following a parent-child separation trauma during childhood: a natural experiment during World War II. Am. J. Hum. Biol. 20, 345–351 (2008).

    PubMed  Google Scholar 

  131. 131.

    Bradley, B. et al. Association between childhood maltreatment and adult emotional dysregulation in a low-income, urban, African American sample: moderation by oxytocin receptor gene. Dev. Psychopathol. 23, 439–452 (2011).

    PubMed  PubMed Central  Google Scholar 

  132. 132.

    McQuaid, R. J., McInnis, O. A., Stead, J. D., Matheson, K. & Anisman, H. A paradoxical association of an oxytocin receptor gene polymorphism: early-life adversity and vulnerability to depression. Front. Neurosci. 7, 128 (2013).

    PubMed  PubMed Central  Google Scholar 

  133. 133.

    Myers, A. J. et al. Variation in the oxytocin receptor gene is associated with increased risk for anxiety, stress and depression in individuals with a history of exposure to early life stress. J. Psychiatr. Res. 59, 93–100 (2014).

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Preparation of this manuscript was supported by US National Institutes of Health (NIH) grants R01MH096983, R01MH112788 and 1P50MH100023 to L.J.Y. and P51OD11132 to the Yerkes National Primate Research Center (YNPRC). The authors thank K. Inoue for his contribution to the manuscript.

Reviewer information

Nature Reviews Neuroscience thanks A. Bonci, O. Bosch and R. Froemke for their contribution to the peer review of this work.

Author information

Affiliations

Authors

Contributions

H.W. and L.J.Y. researched data for the article and made substantial contributions to the discussion of content and to the writing, review and editing of the manuscript before submission.

Corresponding author

Correspondence to Larry J. Young.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Glossary

Hominids

Humans and their ancestors following separation from the Pan clade.

Sociosensory information

Any form of sensory information (for example, olfactory, visual, tactile and auditory) perceived from a social source, typically a conspecific.

Alloparental behaviour

Parental nurturing behaviour (for example, retrieving, licking and grooming) exhibited towards a non-descendent infant or juvenile.

Odorant coding

The transduction of odours into distinct neural signals in the olfactory bulb and downstream pathways, which enables an organism to distinguish complex odours and associate an odour or its source with reinforcers.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Walum, H., Young, L.J. The neural mechanisms and circuitry of the pair bond. Nat Rev Neurosci 19, 643–654 (2018). https://doi.org/10.1038/s41583-018-0072-6

Download citation

Further reading

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