Rethinking the Architecture of Attachment: New Insights into the Role for Oxytocin Signaling

Abstract

Social attachments, the enduring bonds between individuals and groups, are essential to health and well-being. The appropriate formation and maintenance of social relationships depend upon a number of affective processes, including stress regulation, motivation, reward, as well as reciprocal interactions necessary for evaluating the affective state of others. A genetic, molecular, and neural circuit level understanding of social attachments therefore provides a powerful substrate for probing the affective processes associated with social behaviors. Socially monogamous species form long-term pair bonds, allowing us to investigate the mechanisms underlying attachment. Now, molecular genetic tools permit manipulations in monogamous species. Studies using these tools reveal new insights into the genetic and neuroendocrine factors that design and control the neural architecture underlying attachment behavior. We focus this discussion on the prairie vole and oxytocinergic signaling in this and related species as a model of attachment behavior that has been studied in the context of genetic and pharmacological manipulations. We consider developmental processes that impact the demonstration of bonding behavior across genetic backgrounds, the modularity of mechanisms underlying bonding behaviors, and the distributed circuitry supporting these behaviors. Incorporating such theoretical considerations when interpreting reverse genetic studies in the context of the rich ethological and pharmacological data collected in monogamous species provides an important framework for studies of attachment behavior in both animal models and studies of human relationships.

Oxytocin receptor function regulates neural signatures of pair bonding and fidelity in the nucleus accumbens

“…Alternatively, or in combination, such sex differences in the NAc may arise from Oxtrregulated inputs to this region that differ between males and females 3,4,[58][59][60][61][67][68][69] . Consistent with this model, circuits that differ between the sexes influence the function of less dimorphic brain regions to generate sex-typical neural activity and behavior across species [70][71][72] the NAc between males and females may reflect that Oxtr signaling and other neuromodulatory pathways facilitating pair bonding evolved in prairie voles to act on ancestral, sexually dimorphic neural circuits 13,73,74 . Such neuromodulation may thus influence these pathways in prairie voles and other monogamous species to generate more monomorphic and synchronized reciprocal patterns of behavior to promote long-term attachment between mates 20,75-83 .…”

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

“…While nonapeptide systems were not the focus of the current study, an intriguing follow-up question is how much of the pair bond transcription and its maintenance is attributable to nonapeptide dynamics. Recent publication of pair bond formation in Oxtr null voles provides a unique opportunity to identify oxytocin-dependent and independent transcriptional changes that support pair bonds ( Berendzen and Manoli, 2022 ).…”

Effects of oxytocin ablation on pup rescue, nursing behaviors and response to pup separation in early‐to‐mid postpartum mice

“…The percentage of adult female prairie voles that display maternal behaviors is variable (18%–50%), and is dependent on rearing social conditions 46,47 . In this species, genetic ablation of oxytocin receptor using the clustered regularly interspaced short palindromic repeats (CRISPR) technique yielded striking results: the oxytocin receptor null prairie voles with no binding activity with 125 I‐OVTA were intact for maternal and paternal behaviors and pair bonding 41,48 . Mutant mothers were also able to transfer some milk to suckling infants, resulting in the survival of approximately half the litter, although their mean body weight was significantly reduced.…”

“…46,47 In this species, genetic ablation of oxytocin receptor using the clustered regularly interspaced short palindromic repeats (CRISPR) technique yielded striking results: the oxytocin receptor null prairie voles with no binding activity with 125 I-OVTA were intact for maternal and paternal behaviors and pair bonding. 41,48 Mutant mothers were also able to transfer some milk to suckling infants, resulting in the survival of approximately half the litter, although their mean body weight was significantly reduced. Oxytocin receptor KO prairie voles were also created independently and it was reported that they exhibited reduced preference for social novelty and learning of peer-helping behavior and increased repetitive behaviors.…”