Partner separation rescues pair bond-induced decreases in hypothalamic oxytocin neural densities

Abstract

Studies in prairie voles (Microtus ochrogaster) have shown that although formation of the pair bond is accompanied by a suite of behavioral changes, a bond between two voles can dissolve and individuals can form new pair bonds with other conspecifics. However, the neural mechanisms underlying this behavioral flexibility have not been well-studied. Here we examine plasticity of nonapeptide, vasopressin (VP) and oxytocin (OT), neuronal populations in relation to bonding and the dissolution of bonds. Using adult male and female prairie voles, animals were either pair bonded, co-housed with a same-sex sibling, separated from their pair bond partner, or separated from their sibling. We examined neural densities of VP and OT cell groups and observed plasticity in the nonapeptide populations of the paraventricular nucleus of the hypothalamus (PVN). Voles that were pair bonded had fewer PVN OT neurons, suggesting that PVN OT neural densities decrease with pair bonding, but increase and return to a pre-pair bonded baseline after the dissolution of a pair bond. Our findings suggest that the PVN nonapeptide cell groups are particularly plastic in adulthood, providing a mechanism by which voles can exhibit context-appropriate behavior related to bond status.

Aging leads to sex-dependent effects on pair bonding and increased number of oxytocin-producing neurons in monogamous prairie voles

“…Females display a host of isolation-induced phenotypes, including anhedonia, increased anxiety-like phenotypes and aggression, and neuroendocrine disruption (Grippo et al, 2008, 2007; McNeal et al, 2014; Scotti et al, 2015; Watanasriyakul et al, 2022). One study reported persistence of pair bonds following 4 wks separation, without any effect of sex in ∼2-6 month old voles (Fricker et al, 2023). In our experiments, partner preference after 4 wks separation followed a U-curve, where 6- and 18-month females demonstrated a strong partner preference, but 12-month animals did not.…”

“…Furthermore, direct manipulation of these circuits can facilitate or inhibit pair bonding in prairie voles, and can even produce bonding in typically promiscuous species (Keebaugh et al, 2015; Lim et al, 2004; Lim and Young, 2004; Ross et al, 2009; Winslow et al, 1993; Young et al, 2001). Dynamic changes in oxytocin and vasopressin circuitry occur across postnatal development and in response to pair bonding, pup rearing, and partner separation (Audunsdottir and Quintana, 2022; Ebner et al, 2013; Fliers et al, 1985; Fricker et al, 2023; Hiura et al, 2023; Hiura and Ophir, 2018; Ishunina and Swaab, 1999; Kelly et al, 2018, 2017; Kenkel et al, 2019). However, the vast majority of experimentation on pair bonding and its component neurochemical systems is performed in young adult voles.…”

“…Animals were tested 2 days (short-term) and 2 wks (long-term) following pairing to examine whether age impacts the development of pair bonds (Brusman et al, 2021). We then separated pairs for 4 weeks before testing for bond persistence following partner loss via partner preference and free interaction tests (Fricker et al, 2023; Sadino et al, 2021). Finally, we investigated the potential neurochemical mechanisms underlying the evolution of pair bonds dynamics during aging by quantifying the number of oxytocin and vasopressin cells in the PVH.…”

Prairie voles as a model for adaptive reward remodeling following loss of a bonded partner

“…Males and females who were paired for 2 or more weeks prior to separation retained their partner preference for at least 4 weeks of separation. 49,120 For shorter pairing periods, pair bonds were not always retained. 54,121 In tests that enable short, repeated rounds of partner or novel interaction after 4 weeks of separation, female voles with long-term bonds exhibited dramatically reduced partner-directed huddling.…”

“…49 Bonding also results in changes in oxytocin systems that revert upon long-term separation. 54,120 In both male and female voles, partner separation increases the number of oxytocin immunoreactive cells in the periventricular nucleus to the level of sexually naïve same-sex sibling pairs. 120 This remodeling of social reward systems may ultimately be key indicators of loss adaptation.…”