Prairie Voles as a Model for Understanding the Genetic and Epigenetic Regulation of Attachment Behaviors

Abstract

Over a lifetime, humans build relationships with family, friends, and partners that are critically important for our mental and physical health. Unlike commonly used laboratory mice and rats, Microtine rodents provide a unique model to study the neurobiology underlying pair bonding and the selective attachments that form between adults. Comparisons between monogamous prairie voles and the closely related but nonmonogamous meadow and montane voles have revealed that brain-region-specific neuropeptide receptor patterning modulates social behavior between and within species. In particular, diversity in vasopressin 1a receptor (V1aR) distribution has been linked to individual and species differences in monogamy-related behaviors such as partner preference, mate guarding, and space use. Given the importance of differential receptor expression for regulating social behavior, a critical question has emerged: What are the genetic and epigenetic mechanisms that underlie brain-region-specific receptor patterns? This review will summarize what is known about how the vasopressin (AVP)-V1aR axis regulates social behaviors via signaling in discrete brain regions. From this work, we propose that brain-region-specific regulatory mechanisms facilitate robust evolvability of V1aR expression to generate diverse sociobehavioral traits. Translationally, we provide a perspective on how these studies have contributed to our understanding of human social behaviors and how brain-region-specific regulatory mechanisms might be harnessed for targeted therapies to treat social deficits in psychiatric disorders such as depression, complicated grief, and autism spectrum disorder.

Comparative role of reward in long-term peer and mate relationships in voles

“…Williams et al, 1992) as well as for familiar same-sex peers (Beery et al, 2018;DeVries et al, 1997). Because of these selective social relationships, prairie voles have been hailed as an emerging model organism for the translational study of human social deficits in disorders such as autism spectrum disorder and schizophrenia (King et al, 2016;Lim et al, 2005;McGraw and Young, 2010;Modi and Young, 2012;Sadino and Donaldson, 2018).…”

Genetic ancestry predicts male-female affiliation in a natural baboon hybrid zone

“…Strong evidence for genetic effects comes from interspecific comparisons between pair-bonded and multiply mating species. For example, comparisons between the monogamous prairie vole and other, closely related promiscuous voles have identified genetic divergence in the pathways that regulate arginine vasopressin, oxytocin, and dopamine signaling, which in turn influences pair-bonding behavior (Young et al, 1996; Young et al, 1999; Young et al, 1997a; Young et al, 1997b; reviewed in Carter & Perkeybile, 2018; Johnson & Young, 2015; Sadino & Donaldson, 2018; Young et al, 2011). These pathway differences may in part be due to differences in the distribution and densities of hormone receptors in the brain, suggesting one important mechanism through which variation in opposite-sex social relationships evolves (Insel & Shapiro, 1992; Insel et al, 1994; Smeltzer et al, 2006).…”

Paternal deprivation impairs social behavior putatively via epigenetic modification to lateral septum vasopressin receptor

“…VP has three identified receptors (V1aR, V1bR, and V2R), and OT has just one (OTR). Most of the research on nonapeptide receptor impacts on social behavior has focused on V1aR and OTR, due, in part, to their wide distribution across several areas of the brain that regulate social behavior and their extensive implication in several areas of social behavior, perhaps most notably pair bonding (16,17). Although the role of V1bR is beginning to emerge as an important modulator of social memory and aggression (18), its distribution appears to be relatively restricted to the hippocampus (HPC) and pituitary, its influence on behavior is comparably nuanced, and the developmental trajectories and sensitivity to early-life experiences of V1bR have not been investigated.…”

“…The rich knowledge of natural history for prairie voles highlights the strength that this species offers toward developing a powerful and ecologically relevant model for translational social neuroscience (17). In an attempt to loosely approximate a real-world tradeoff that parents experience, we raised prairie vole pups (i) in the presence or absence of a father and (ii) with parents that did or did not experience a tradeoff in caring for themselves or caring for their offspring.…”