Interactions of sex and early life social experiences at two developmental stages shape nonapeptide receptor profiles

Abstract

Early life social experiences are critical to behavioral and cognitive development, and can have a tremendous influence on developing social phenotypes. Most work has focused on outcomes of experiences at a single stage of development (e.g. perinatal or post-weaning). Few studies have assessed the impact of social experience at multiple developmental stages and across sex. Oxytocin and vasopressin are profoundly important for modulating social behavior and these nonapeptide systems are highly sensitive to developmental social experience, particularly in brain areas important for social behavior. We investigated whether oxytocin receptor (OTR) and vasopressin receptor (V1aR) distributions of prairie voles (Microtus ochrogaster) change as a function of parental composition within the natal nest or social composition after weaning. We raised pups either in the presence or absence of their fathers. At weaning, offspring were housed either individually or with a same-sex sibling. We also examined whether changes in receptor distributions are sexually dimorphic because the impact of the developmental environment on the nonapeptide system could be sex-dependent. We found that differences in nonapeptide receptor expression were region-specific, sex-specific and rearing condition-specific, indicating a high level of complexity in the ways that early life experiences shape the social brain. We found many more differences in V1aR density compared to OTR density, indicating that nonapeptide receptors demonstrate differential levels of neural plasticity and sensitivity to environmental and biological variables. Our data highlight that critical factors including biological sex and multiple experiences across the developmental continuum interact in complex ways to shape the social brain.

Oxytocin receptor binding in the titi monkey hippocampal formation is associated with parental status and partner affiliation

“…None of the comparisons between males' and females' OXTR binding in any of our regions of interest attained significance. These null findings are consistent with several other investigations in rodents showing no sex differences in hippocampal OXTR binding in many species, including C57BL/6 mice 22,43 , golden hamsters (Mesocricetus auratus) 42 , naked mole rats (Heterocephalus glaber) 44 , Wistar rats 45 , and prairie voles 47 . Although there are well-documented sex differences in hippocampal plasticity (for a comprehensive review, see 76 ), the results of our study may suggest that these plasticity differences are unrelated to OXTR binding in titi monkeys.…”

“…Thus far, sex differences in hippocampal OXTR binding have been studied primarily in rodents, and research has yielded mixed evidence. For example, although seven studies (across six different rodent species) failed to find sex differences in hippocampal OXTR binding 22 , 42 – 47 , two studies (across three rodent species) found that females exhibited higher hippocampal OXTR binding than males 48 , 49 , and two other studies (across two rodent species) found that males exhibited higher hippocampal OXTR binding than females 50 , 51 . In humans, two studies investigated OXTR binding in the basal forebrain and midbrain in post-mortem brain tissue, and neither found sex differences in any of the regions that were studied 52 , 53 .…”

Social status in mouse social hierarchies is associated with variation in oxytocin and vasopressin 1a receptor densities

“…Thirdly, the observed receptor binding differences may reflect experience-dependent changes in the expression of receptors induced via the differential social environments experienced by dominant and subordinate animals. Previous work has established that variation in social environments can induce such changes in the distribution of both OTR and V1aR (Curley et al, 2009;Hiura and Ophir, 2018;Prounis et al, 2015;Winslow et al, 1993). In addition to changes in aggressive and subordinate behaviors displayed by mice of different social ranks, individuals also show plastic changes in several other behaviors.…”

Editorial: What's Love Got to Do With It: The Evolution of Monogamy

“…Finally, ontogenetic effects on monogamy have received comparably little attention compared to Tinbergen’s other levels of analysis, though such studies do exist. For example, rodent studies have clearly demonstrated that early-life experience can alter the propensity for monogamy ( Bales et al, 2007 ; Ahern and Young, 2009 ; Prounis et al, 2015 ), and the neurochemical substrates that contribute to it ( Hiura and Ophir, 2018 ; Hiura et al, 2018 ; Kelly et al, 2018 ; Prounis et al, 2018 ). Similarly, Al-Naimi et al examines the effects of social and environmental disruptions in the life of young animals, and discuss how these may affect the tendency of males to behave monogamously.…”