Prolonged partner separation erodes nucleus accumbens transcriptional signatures of pair bonding in male prairie voles
- University of Colorado Boulder, United States
- Oregon Health and Science University Hospital, United States
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.
-
Supplemental Data 1FigShare, 10.6084/m9.figshare.19911541.
-
Supplemental Data 2FigShare, 10.6084/m9.figshare.19911577.
-
Supplemental Data 3FigShare, 10.6084/m9.figshare.19911583.
-
Custom python script for scoring partner preference videosGitHub.com/donaldsonlab/CleversysSummaryRearranger.
Article and author information
Author details
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.
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.
Metrics
-
- 1,755
- views
-
- 235
- downloads
-
- 11
- citations
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)
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
Further reading
-
- Neuroscience
When mice run, activity in their primary visual cortex (V1) is strongly modulated. This observation has altered conceptions of a brain region assumed to be a passive image processor. Extensive work has followed to dissect the circuits and functions of running-correlated modulation. However, it remains unclear whether visual processing in primates might similarly change during locomotion. We therefore measured V1 activity in marmosets while they viewed stimuli on a treadmill. In contrast to mouse, running-correlated modulations of marmoset V1 were small and tended to be slightly suppressive. Population-level analyses revealed trial-to-trial fluctuations of shared gain across V1 in both species, but while strongly correlated with running in mice, gain modulations were smaller and more often negatively correlated with running in marmosets. Thus, population-wide fluctuations of V1 may reflect a common feature of mammalian visual cortical function, but important quantitative differences point to distinct consequences for the relation between vision and action in primates versus rodents.
-
- Neuroscience
Significant technical challenges exist when measuring synaptic connections between neurons in living brain tissue. The patch clamping technique, when used to probe for synaptic connections, is manually laborious and time-consuming. To improve its efficiency, we pursued another approach: instead of retracting all patch clamping electrodes after each recording attempt, we cleaned just one of them and reused it to obtain another recording while maintaining the others. With one new patch clamp recording attempt, many new connections can be probed. By placing one pipette in front of the others in this way, one can ‘walk’ across the mouse brain slice, termed ‘patch-walking.’ We performed 136 patch clamp attempts for two pipettes, achieving 71 successful whole cell recordings (52.2%). Of these, we probed 29 pairs (i.e. 58 bidirectional probed connections) averaging 91 μm intersomatic distance, finding three connections. Patch-walking yields 80–92% more probed connections, for experiments with 10–100 cells than the traditional synaptic connection searching method.
