How prior pair-bonding experience affects future bonding behavior in monogamous prairie voles.

Monogamous prairie voles (Microtus ochrogaster) form mating-based pair bonds. Although wild prairie voles rarely re-pair following loss of a partner, laboratory studies have shown that previous pairing and mating does not negate the ability to form a new partner preference. However, little is known about how prior bond experience may alter the trajectory and display of a new pair bond. In the present study, we disrupted an initial pair bond by separating partners and then varied the amount of time before a new partner was introduced. We assessed how separation time affected the stability of partner preference over time and influenced decision-making in male voles performing a head-to-head partner preference test in which they chose between the first and second partner. We found that the ability to consistently display a preference for the second partner, supplanting the initial pair bond, depended on how long the test animal was separated from their first partner. Prior bonding experience also shaped the subsequent effects of mating on partner preference. Partner preference strength was sensitive to latency to mate with the second partner but not the first partner, irrespective of separation time. These results suggest that the ability to form a consistent, strong preference for a new partner after an initial pair bond depends upon the amount of time that has passed since separation from the first partner. These results provide valuable insight into how social bonds are dynamically shaped by prior social experience and identify variables that contribute to recovery from partner loss and the ability to form a new pair bond. They also delineate a behavioral trajectory essential for future work examining the hormonal and genetic changes that enable recovery from partner loss.

Developmental disruption of amygdala transcriptome and socioemotional behavior in rats exposed to valproic acid prenatally.

BACKGROUND: The amygdala controls socioemotional behavior and has consistently been implicated in the etiology of autism spectrum disorder (ASD). Precocious amygdala development is commonly reported in ASD youth with the degree of overgrowth positively correlated to the severity of ASD symptoms. Prenatal exposure to VPA leads to an ASD phenotype in both humans and rats and has become a commonly used tool to model the complexity of ASD symptoms in the laboratory. Here, we examined abnormalities in gene expression in the amygdala and socioemotional behavior across development in the valproic acid (VPA) rat model of ASD. METHODS: Rat dams received oral gavage of VPA (500 mg/kg) or saline daily between E11 and 13. Socioemotional behavior was tracked across development in both sexes. RNA sequencing and proteomics were performed on amygdala samples from male rats across development. RESULTS: Effects of VPA on time spent in social proximity and anxiety-like behavior were sex dependent, with social abnormalities presenting in males and heightened anxiety in females. Across time VPA stunted developmental and immune, but enhanced cellular death and disorder, pathways in the amygdala relative to saline controls. At postnatal day 10, gene pathways involved in nervous system and cellular development displayed predicted activations in prenatally exposed VPA amygdala samples. By juvenile age, however, transcriptomic and proteomic pathways displayed reductions in cellular growth and neural development. Alterations in immune pathways, calcium signaling, Rho GTPases, and protein kinase A signaling were also observed. CONCLUSIONS: As behavioral, developmental, and genomic alterations are similar to those reported in ASD, these results lend support to prenatal exposure to VPA as a useful tool for understanding how developmental insults to molecular pathways in the amygdala give rise to ASD-related syndromes.