1. Neuroscience

Prolonged partner separation erodes nucleus accumbens transcriptional signatures of pair bonding in male prairie voles

  1. Julie M Sadino
  2. Xander G Bradeen
  3. Conor J Kelly
  4. Liza E Brusman
  5. Deena M Walker
  6. Zoe R Donaldson  Is a corresponding author
  1. University of Colorado Boulder, United States
  2. Oregon Health and Science University Hospital, United States
https://doi.org/10.7554/eLife.80517
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Cite this article
  1. Julie M Sadino
  2. Xander G Bradeen
  3. Conor J Kelly
  4. Liza E Brusman
  5. Deena M Walker
  6. Zoe R Donaldson
(2023)
Prolonged partner separation erodes nucleus accumbens transcriptional signatures of pair bonding in male prairie voles
eLife 12:e80517.
https://doi.org/10.7554/eLife.80517
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Abstract

The loss of a spouse is often cited as the most traumatic event in a person's life. However, for most people, the severity of grief and its maladaptive effects subside over time via an understudied adaptive process. Like humans, socially monogamous prairie voles (Microtus ochrogaster) form opposite-sex pair bonds, and upon partner separation, show stress phenotypes that diminish over time. We test the hypothesis that extended partner separation diminishes pair bond-associated behaviors and causes pair bond transcriptional signatures to erode. Pairs were cohoused for 2 weeks and then either remained paired or were separated for 48hrs or 4wks before collecting fresh nucleus accumbens tissue for RNAseq. In a separate cohort, we assessed partner-directed affiliation at these time points. We found that these behaviors persist despite prolonged separation in both same-sex and opposite-sex paired voles. Opposite-sex pair bonding led to changes in accumbal transcription that were stably maintained while animals remained paired but eroded following prolonged partner separation. Eroded genes are associated with gliogenesis and myelination, suggesting a previously undescribed role for glia in pair bonding and loss. Further, we pioneered neuron-specific translating ribosomal affinity purification in voles. Neuronally-enriched transcriptional changes revealed dopaminergic-, mitochondrial-, and steroid hormone signaling-associated gene clusters sensitive to acute pair bond disruption and loss adaptation. Our results suggest that partner separation erodes transcriptomic signatures of pair bonding despite core behavioral features of the bond remaining intact, revealing potential molecular processes priming a vole to be able to form a new bond.

Data availability

All sequencing data is available on GEO (GSE192661). All lab specific code is available on the Donaldson Lab GitHub (https://github.com/donaldsonlab) and all metadata including comprehensive statistical analyses, animal information, differential gene expression, gene sets, and IPA analyses are available on the Donaldson lab Figshare (DOIs in Supplemental) . The vole optimized DIO-eGFP-RPL10a vector will be made available on Addgene.

The following data sets were generated

Article and author information

Author details

  1. Julie M Sadino

    Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Xander G Bradeen

    Department of Psychology and Neuroscience, University of Colorado Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Conor J Kelly

    Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2410-7892

  4. Liza E Brusman

    Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Deena M Walker

    Department of Behavioral Neuroscience, Oregon Health and Science University Hospital, Portland, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Zoe R Donaldson

    Department of Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, United States
    For correspondence
    zoe.donaldson@colorado.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6699-7905

Funding

National Institutes of Health (T32 GM008759-17/18)

  • Julie M Sadino

Dana Foundation

  • Zoe R Donaldson

Whitehall Foundation

  • Zoe R Donaldson

National Institutes of Health (DP2OD026143)

  • Zoe R Donaldson

National Institutes of Health (R01MH125423)

  • Zoe R Donaldson

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All procedures were performed in accordance with standard ethical guidelines (National Institutes of Health Guide for the Care and Use of Laboratory Animals) and approved by the Institutional Animal Care and Use Committee (IACUC) at the University of Colorado Boulder (protocol #2435). For stereotaxic surgery, adult prairie voles were anesthetized using isoflurane (3% induction, 1-2.5% maintenance) and depth of anesthesia was monitored by breathing and toe pinch reflex.

Reviewing Editor

  1. Margaret M McCarthy, University of Maryland School of Medicine, United States

Publication history

  1. Received: May 24, 2022
  2. Accepted: February 27, 2023
  3. Accepted Manuscript published: February 28, 2023 (version 1)
  4. Accepted Manuscript updated: March 22, 2023 (version 2)
  5. Accepted Manuscript updated: March 23, 2023 (version 3)

Copyright

© 2023, Sadino et al.

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

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  1. Julie M Sadino
  2. Xander G Bradeen
  3. Conor J Kelly
  4. Liza E Brusman
  5. Deena M Walker
  6. Zoe R Donaldson
(2023)
Prolonged partner separation erodes nucleus accumbens transcriptional signatures of pair bonding in male prairie voles
eLife 12:e80517.
https://doi.org/10.7554/eLife.80517

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