Paternal deprivation affects social behaviors and neurochemical systems in the offspring of socially monogamous prairie voles

Fujisaku

2020

J Neuroendocrinology

Autism spectrum disorder (ASD) is a neurodevelopmental disorder estimated by the World Health Organization to occur in one of 160 children worldwide. No pharmaceutical treatments are available to improve the deficits in social communication that are common symptoms of ASD. Recent clinical trials have focused on the nasal application of oxytocin, a neuronal peptide known to regulate a variety of social behaviours. However, the effect of oxytocin on this deficit is inconclusive. By contrast, evidence from ASD animal model studies indicates that when animals are treated with oxytocin during early development, improvements in social deficits are observed in adulthood. Thus, it is necessary to examine the effect of therapeutic target medication prescribed in early development. Mice prenatally exposed to valproic acid (VPA) are widely used as an animal model of ASD. However, many behavioural studies have been conducted during adulthood rather than early development. To establish a screening system to identify therapeutic drugs that are effective when delivered during the early postnatal period, it is important to examine the early developmental changes in their communicative behaviours. In the present study, we examined the ultrasonic vocalisation (USV) of VPA-exposed mice pups during their early postnatal developmental days. USV rates were comparable to those of the controls until the first week of their life but declined more on postnatal day 11. We checked the expression of oxytocin system in the hypothalamus and found the down-regulation of oxytocin and CD38, and up-regulation of oxytocin receptor in the VPA pups. Acute administration of oxytocin on postnatal day 11 increased the call rate of VPA pups.Taken together, we have demonstrated there was a deficiency in the oxytocinergic signalling in the VPA pups and also shown the existence of time periods that are effective with respect to screening the therapeutic drugs. K E Y W O R D Sautism spectrum disorder, early neurodevelopment, oxytocin, valproic acid mouse model

Section: Introductionmentioning

confidence: 99%

Oxytocin ameliorates maternal separation‐induced ultrasonic vocalisation calls in mouse pups prenatally exposed to valproic acid

Fujisaku

2020

J Neuroendocrinology

“…Variation in parental composition (such as manipulating the presence or absence of fathers during the rearing period) has been shown to alter the rate at which prairie vole pups develop (Wang & Novak 1992). This variation also impacts social affiliation towards conspecifics in adulthood (Tabbaa et al 2017) and the species-typical pair-bonding behavior of adult animals (Ahern & Young 2009).…”

Section: Introductionmentioning

confidence: 99%

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

Hiura

Ophir

2018

Integrative Zoology

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.

“…In California mice, removal of the father 3 days postpartum had no effect on the anxiety of the adult offspring tested in an empty open-field arena, but the subjects showed reduced social interactions and increased aggression (Bambico et al, 2015). In prairie voles, removal of the father a day after birth had no effect on the anxiety levels of adult offspring tested on the elevated plus maze but increased their social affiliation toward a conspecific (Tabbaa et al, 2017). However, with removal of the father 2 days before birth, the adult offspring displayed delayed partner preference and were less parental.…”

Section: Discussionmentioning

confidence: 90%

Socio-Ecological Disruptions at Critical Periods During Development Alter Stress Responses and Hippocampal Dendritic Morphology of Prairie Voles: Implications for Social Monogamy

et al. 2018

Emotions are often associated with the evolution of monogamy. For example, fear of cuckoldry has been recently proposed as the driving force for human monogamy. We used prairie voles (Microtus ochrogaster) as a model of human behavior to study how stress reactivity is shaped by socio-ecological disruptions experienced as neonates and as subadults. We hypothesized that social disruptions would have a greater impact on the vole's stress levels than ecological disruptions, and that females would be more susceptible to the experience than males. At 6 days postpartum, the housing conditions were manipulated to have offspring raised by: (1) both parents under a protective cover (NoDisrupt); (2) Both parents uncovered (EcoDisrupt); (3) Mother alone covered (SocDisrupt); (4) Mother alone uncovered (SocEcoDisrupt). To experience disruptions as subadults, offspring were weaned then housed either alone (Isolate) or with a same-sex sibling (Social). As adults, each offspring was placed in an open-field arena and tested over 3 consecutive days to measure its behavior in response to an empty space (Day1), a same-sex vole in a container (Day2), and an empty container (Day3). The brain of a subgroup of subjects was processed for Golgi staining to assess the impact of disruptions on hippocampal dendritic morphology in adulthood. Males that experienced social disruption in early life displayed lower stress levels on Day2 of testing than males and females in other groups. This effect was only evident in males that did not experience social disruptions as subadults. Socio-ecological disruptions at postpartum had an unanticipated impact on the hippocampus of the voles. The apical dendrites of the CA3 neurons in male and female voles that experienced either social or ecological disruptions in early life and remained socially isolated as subadults were longer than those in undisturbed voles. Our results suggest that social disruptions experienced in early life modulate the male's stress-related behaviors and may thus influence his monogamous tendencies. Exposure to disruptions may also impact the memory circuits of the brain that monogamous animals use to make mating decisions.