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 behavioral and neuroendocrine stress phenotypes that diminish over time. Eventually, they can form a new bond, a key indicator of adapting to the loss of their partner. Thus, prairie voles provide an ethologically-relevant model for examining neuromolecular changes that emerge following partner separation for adapting to loss. Here, we test the hypothesis that extended partner separation diminishes pair bond-associated behaviors (partner preference and selective aggression) 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 preference and selective aggression at these time points. Surprisingly, pair bond-associated behaviors persist despite prolonged separation and are similar between same-sex and opposite-sex paired voles. In contrast, we found that opposite-sex pair bonding, as compared with same-sex pairing, led to changes in accumbal transcription that were stably maintained as long as animals remained paired but eroded following prolonged partner separation. Eroded genes are primarily associated with gliogenesis and myelination, suggesting a previously undescribed role for glia in maintaining pair bonds and adapting to partner loss. We further reasoned that relevant neuronal transcriptional changes may have been masked by the prominent transcriptional signals associated with glia. Thus, we pioneered neuron-specific translating ribosomal affinity purification in voles. Neuronally-enriched transcriptional changes revealed dopaminergic-, mitochondrial-, and steroid hormone signaling-associated gene clusters whose expression patterns are sensitive to acute pair bond disruption and loss adaptation. Together, our results suggest that partner separation results in erosion of transcriptomic signatures of pair bonding despite core behavioral features of the bond remaining intact, revealing potential molecular processes central to priming a vole to be able to form a new bond.
