Prairie Voles: Recovering from a broken heart

A molecular signature found in the brains of monogamous prairie voles begins to decay after prolonged separation from their partner.
  1. Alison M Bell  Is a corresponding author
  1. Department of Evolution, Ecology and Behavior, University of Illinois, United States

Despite the best efforts of my hole-digging dog, my backyard is home to rodents who are in love. Furry prairie voles spend lots of time huddled underground, usually in pairs that work together to rear their pups. If the couple is separated, even for as long as two weeks, they still remain bonded and will reunite as tight as they were before (Getz et al., 1981). These humble rodents are famous for their monogamous behavior, and have been the subject of many eye-catching headlines (Tucker, 2014; Armitage, 2015). Part of their appeal is the possibility to understand the biological basis of love, devotion, and life-long attachment – topics that seem more suited to humanities than biology departments.

Most scientific research on prairie voles has focused on how monogamous pairs are formed, particularly the role of oxytocin, the famous ‘love hormone’ (Insel and Shapiro, 1992). However, less is known about what happens when these bonds get broken; what happens when one member of the pair outlives the other? Previous behavioral studies have shown that voles exhibit signs of distress when they are separated from their partner, but eventually adapt to this loss and seek out a new connection (Harbert et al., 2020). Now, in eLife, Zoe Donaldson and colleagues from the University of Colorado Boulder and Oregon Health and Science University – including Julie Sadino as first author – report what happens to voles as they recover from a broken heart (Sadino et al., 2023).

Sadino et al. studied male voles in same-sex and opposite sex pairs that had been housed together for two weeks and then separated for 48 hours or four weeks. Using a technique called vTRAP (short for translating ribosome affinity purification), they investigated which genes are expressed in the nucleus accumbens, a part of the brain that is engaged during pair formation in mammals, including humans (Walum and Young, 2018). The pattern of genes expressed (also known as the transcriptional signature) was measured before and after voles were separated, along with their behavior to see if these two factors are coordinated together. The female voles were also prevented from becoming pregnant to control for the potentially confounding influence of co-parenting together.

The experiments revealed that male voles stably express hundreds of genes in their nucleus accumbens when living with a partner, which remained unchanged even after the pair were separated for a few days. However, while the male voles continued to prefer the company of their partner even after long periods apart, the transcriptional signature in the nucleus accumbens started to decay as the voles spent more time away from each other.

These findings suggest that genes in the brains of the voles start to alter their expression before the voles lose preference for their old mate. This means that although voles may behaviorally resume their relationship after long periods of separation, elements of their transcriptome may be less optimistic that this reunion will happen. It is tempting to speculate that the genes that begin to change expression may somehow be involved in recovering from the loss of a partner.

Furthermore, while behavioral and genomic changes in the brain occurring over different timescales is not an entirely new finding (White et al., 2002), the results of Sadino et al. do offer some clues as to how this may work at a mechanistic level. For example, genes that were upregulated in bonded males, but downregulated after a few weeks of separation, follow a pattern that suggests they may have a role in coping with loss. In contrast, another set of genes, which was initially downregulated and then upregulated after weeks of separation, may be involved in helping to prime the vole to form a new bond.

Understanding the neural basis of complex social behaviors is a hard problem. However, the work by Sadino et al. – which uses a savvy experimental design to connect genes, the brain and animal behavior – shows how it can be done. Moreover, and somewhat surprisingly, other researchers recently reported that prairie voles do not require a receptor for oxytocin in order to form social attachments (Berendzen et al., 2023). It seems that there are actually many players coordinating this complex social behavior.

An immediate task for future work is to look at brain areas other than the nucleus accumbens, which is closely associated with reward. While pair bonding is rewarding, this may be independent from the cognitive aspects of separation, such as the memory of a lost companion or the willingness to find a new partner. Another priority is to explicitly connect the transcriptional signatures identified with the formation or degradation of the pair bond using functional tests, a challenge the scientific community studying these furry lovers is no doubt going after next.


  1. Book
    1. Tucker A
    What Can Rodents Tell Us about Why Humans Love?
    Smithsonian Magazine.

Article and author information

Author details

  1. Alison M Bell

    Alison M Bell is in the Department of Evolution, Ecology and Behavior, University of Illinois, Urbana-Champaign, United States

    For correspondence
    Competing interests
    No competing interests declared
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8933-8494

Publication history

  1. Version of Record published: April 18, 2023 (version 1)


© 2023, Bell

This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.


  • 1,215
  • 50
  • 1

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Alison M Bell
Prairie Voles: Recovering from a broken heart
eLife 12:e87550.

Further reading

    1. Neuroscience
    Ece Kaya, Sonja A Kotz, Molly J Henry
    Research Article

    Dynamic attending theory proposes that the ability to track temporal cues in the auditory environment is governed by entrainment, the synchronization between internal oscillations and regularities in external auditory signals. Here, we focused on two key properties of internal oscillators: their preferred rate, the default rate in the absence of any input; and their flexibility, how they adapt to changes in rhythmic context. We developed methods to estimate oscillator properties (Experiment 1) and compared the estimates across tasks and individuals (Experiment 2). Preferred rates, estimated as the stimulus rates with peak performance, showed a harmonic relationship across measurements and were correlated with individuals’ spontaneous motor tempo. Estimates from motor tasks were slower than those from the perceptual task, and the degree of slowing was consistent for each individual. Task performance decreased with trial-to-trial changes in stimulus rate, and responses on individual trials were biased toward the preceding trial’s stimulus properties. Flexibility, quantified as an individual’s ability to adapt to faster-than-previous rates, decreased with age. These findings show domain-specific rate preferences for the assumed oscillatory system underlying rhythm perception and production, and that this system loses its ability to flexibly adapt to changes in the external rhythmic context during aging.

    1. Neuroscience
    Elissavet Chartampila, Karim S Elayouby ... Helen E Scharfman
    Research Article

    Maternal choline supplementation (MCS) improves cognition in Alzheimer’s disease (AD) models. However, the effects of MCS on neuronal hyperexcitability in AD are unknown. We investigated the effects of MCS in a well-established mouse model of AD with hyperexcitability, the Tg2576 mouse. The most common type of hyperexcitability in Tg2576 mice are generalized EEG spikes (interictal spikes [IIS]). IIS also are common in other mouse models and occur in AD patients. In mouse models, hyperexcitability is also reflected by elevated expression of the transcription factor ∆FosB in the granule cells (GCs) of the dentate gyrus (DG), which are the principal cell type. Therefore, we studied ΔFosB expression in GCs. We also studied the neuronal marker NeuN within hilar neurons of the DG because reduced NeuN protein expression is a sign of oxidative stress or other pathology. This is potentially important because hilar neurons regulate GC excitability. Tg2576 breeding pairs received a diet with a relatively low, intermediate, or high concentration of choline. After weaning, all mice received the intermediate diet. In offspring of mice fed the high choline diet, IIS frequency declined, GC ∆FosB expression was reduced, and hilar NeuN expression was restored. Using the novel object location task, spatial memory improved. In contrast, offspring exposed to the relatively low choline diet had several adverse effects, such as increased mortality. They had the weakest hilar NeuN immunoreactivity and greatest GC ΔFosB protein expression. However, their IIS frequency was low, which was surprising. The results provide new evidence that a diet high in choline in early life can improve outcomes in a mouse model of AD, and relatively low choline can have mixed effects. This is the first study showing that dietary choline can regulate hyperexcitability, hilar neurons, ΔFosB, and spatial memory in an animal model of AD.