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

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.

Core Self-Evaluation Moderates Distinctive Similarity Preference in Ideal Partner’s Personality

This research investigated the moderation effects of core self-evaluation (CSE) on singles’ ideal partner preference, concerning distinctive similarity in personality. The data were collected from singles from three countries (i.e., China, Denmark, and US), and modelled in a multilevel profile analysis. The results show that CSE moderated distinctive profile similarity preference in that people high in CSE preferred higher distinctive profile similarity with their ideal partner. In addition, CSE moderated distinctive trait similarity preference in Emotionality, Extraversion, Agreeableness, and Conscientiousness in that people high in CSE preferred their ideal partner to share higher distinctive similarity on these four traits. Implications and limitations of the research and findings are also discussed.

Prenatal Androgen Excess Impairs Sexual Behavior in Adult Female Mice: Perspective on Sexual Dysfunction in PCOS

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders worldwide, affecting 5-20% of reproductive aged women [1]. PCOS is characterised by androgen excess, oligo- or anovulation, and polycystic ovarian morphology [1]. PCOS patients also experience sexual dysfunction, including decreased sexual desire, increased sexual dissatisfaction and gender dysphoria [2-4]. The origins of PCOS-related sexual difficulties remain unidentified, but may be related to impaired central mechanisms regulating sexual behaviours. Prenatally androgenized (PNA) mice recapitulate the PCOS phenotype and exhibit alterations in the neuronal network regulating reproductive function [5], providing a powerful, pathology-based model to unravel the biological origins of sexual dysfunction in PCOS. Here, we aimed to determine whether female sexual behaviours are impaired in the PNA mouse model of PCOS. To model PCOS, female dams received injections of dihydrotestosterone (PNA) or oil vehicle (VEH) daily from gestational day 16-18. Adult female offspring were ovariectomized and implanted with a silastic capsule of estradiol to examine the female-typical sexual behaviour: lordosis as well as partner preference. We also examined a potential masculinisation of the brain by replacing the estradiol implant by a testosterone implant then testing the female for male-like sexual behaviours. PNA females exhibited significantly reduced lordosis behaviour compared to VEH females (p<0.01). In contrast, partner preference and male-like sexual behaviour were not different between PNA and VEH females. In addition, using Open-field test and elevated-plus maze, we observed no effect of prenatal androgen exposure on locomotion and anxiety. These results highlight, for the first time, that prenatal exposure to the non-aromatisable androgen, DHT, impairs female receptivity only without masculinisation. These findings support the use of the PNA mouse model of PCOS to identify the neuronal targets of prenatal androgen action and to determine the mechanisms by which prenatal androgen excess impairs lordosis. Taken together, this study introduce a novel perspective on the origins of sexual dysfunction in women with PCOS and indicate the need for further investigation into the mechanisms of androgen excess on the female brain and sexual function. [1] Lizneva D et al, Fertil Steril. 2016;106:6-15. [2] Fliegner M et al, Geburtshilfe Frauenheilkd. 2019;79:498-509.[3] Kowalczyk R et al, Acta Obstet Gynecol Scand. 2012;91:710-4.[4] Mansson M et al, Eur J Obstet Gynecol Reprod Biol. 2011;155:161-5. [5] Ruddenklau A, Campbell RE. Endocrinology. 2019 Oct 1;160(10):2230-2242.

Brain functional networks associated with social bonding in monogamous voles

Previous studies have related pair-bonding in Microtus ochrogaster, the prairie vole, with plastic changes in several brain regions. However, the interactions between these socially relevant regions have yet to be described. In this study, we used resting-state magnetic resonance imaging to explore bonding behaviors and functional connectivity of brain regions previously associated with pair-bonding. Thirty-two male and female prairie voles were scanned at baseline, 24 hr, and 2 weeks after the onset of cohabitation. By using network-based statistics, we identified that the functional connectivity of a corticostriatal network predicted the onset of affiliative behavior, while another predicted the amount of social interaction during a partner preference test. Furthermore, a network with significant changes in time was revealed, also showing associations with the level of partner preference. Overall, our findings revealed the association between network-level functional connectivity changes and social bonding.